[Adaptation possibility of chosen aspects of pharmaceutical marketing for realization of promotion in health care].
Reform of health service in Poland introduced reliable economic bill and elements of competition among its subjects as well. It created a new situation both for doctors and managers of health service. Need of search for rules and ways of competition exists at present among institutions of health care. Certain solutions can be modelled on the example of pharmaceutical companies already present on the market. As an example of such activities, which they can be applied directly in this new situation may serve so called personal sale and related to it case of institutions the best direct contact between the next but more controversial form of marketing activities worth spreading. The use of direct marketing and advertisements carries most problems with itself. This latter should be easier to accept when it selects an important social aim.


Oceanic plateau of the Hawaiian mantle plume head subducted to the uppermost lower mantle.
The Hawaiian-Emperor seamount chain that includes the Hawaiian volcanoes was created by the Hawaiian mantle plume. Although the mantle plume hypothesis predicts an oceanic plateau produced by massive decompression melting during the initiation stage of the Hawaiian hot spot, the fate of this plateau is unclear. We discovered a megameter-scale portion of thickened oceanic crust in the uppermost lower mantle west of the Sea of Okhotsk by stacking seismic waveforms of SS precursors. We propose that this thick crust represents a major part of the oceanic plateau that was created by the Hawaiian plume head ~100 million years ago and subducted 20 million to 30 million years ago. Our discovery provides temporal and spatial clues of the early history of the Hawaiian plume for future plate reconstructions.


Pancreatoduodenectomy - preventing complications.
Increased awareness of periampullary & pancreatic head cancers, and the accompanying improved outcomes following pancreatoduodenectomy (PD), has possibly led to an increase in patients seeking treatment for the same. While there has definitely been a reduction in morbidity rates following PD in the last few decades, this decline has not mirrored the drastic fall in mortality. Amongst the foremost in the factors responsible for this reduction in mortality is the standardization of surgical technique and development of dedicated teams to manage all aspects of this demanding procedure. This review intends to provide the reader with an overview of major complications following this major surgery and measures to prevent them based on the authors' experience.


Simultaneous assay of thioridazine and its major metabolites in plasma at single dosage levels with a novel report of two ring sulfoxides of thioridazine.
A highly sensitive and selective method of analysis of plasma for thioridazine and its major metabolites, including two isomers of the ring sulfoxide, is presented. It is suitable for following the metabolism of thioridazine for 24 hr after a single dose. The method involves extraction of the materials from plasma, high-performance liquid chromatographic separation, and postcolumn oxidation and fluorometric detection. The sensitivity of the method to thioridazine and its metabolites is 2 ng/ml. Recoveries ranged from 87.8 to 100.6% at levels between 20 and 400 ng/ml.


In vivo rabbit eyecup preparation for use in retinal research.
To develop an in vivo rabbit eyecup preparation that preserves neuronal and vascular connections with normal posterior segment contour, permitting direct access to the retina and facilitating retinal microsurgical and neuroscience research. Cyanoacrylate glue was applied to the anterior sclera of six Dutch-belted rabbits before open-sky vitrectomy. The glue was used to harden the compliant scleral wall and to fix it to the surrounding periorbital tissues. A normal contour of the posterior segment was retained in all cases. Vitrectomy under air was successfully accomplished and an extensive removal of the vitreous gel was achieved. Fluorescein angiography revealed normal vascular patency of the retinal vessels after vitrectomy. The proposed modification of the rabbit eyecup retains the normal neurovascular connections and configuration of the retina, making it suitable for retinal microsurgical maneuvers or any procedures in which easy access to anatomically undisturbed retina is required.


Contemporary management of cleft lip and palate in the United Kingdom. Have we reached the turning point?
Babies born with clefts of the lip, and the alveolus or palate, or both, require multidisciplinary, highly specialised treatment from birth to early adulthood. We review the contemporary management of clefts and outline the current treatment protocol adopted by cleft networks in the United Kingdom. We also look at the level of evidence and the restructuring of services that has defined current practice. In light of the recent Cleft Care UK study, we ask whether it is now time to adopt a new philosophy towards the surgical techniques that are used.


OPT-80 eliminates Clostridium difficile and is sparing of bacteroides species during treatment of C. difficile infection.
During a 10-day treatment for Clostridium difficile infection, OPT-80 and vancomycin were comparably effective in reducing C. difficile counts. Bacteroides fragilis group counts appeared unaffected with increasing dosages of OPT-80, whereas vancomycin was markedly suppressive. Retention of components of the normal microflora might lower the risk of recurrent disease.


Clinical characteristics of moderate or severe COVID-19 infection in patients with rheumatic diseases and analysis of risk factors leading to severe disease.
To explore the clinical characteristics of rheumatic disease (RD) patients who suffered from moderate or severe coronavirus disease 2019 (COVID-19) infection and to evaluate risk factors of COVID-19 infection in RD patients. A retrospective analysis was conducted on 148 moderate or severe COVID-19 patients admitted to the First People's Hospital of Suqian Affiliated to Nanjing Medical University, including 74 RD patients and 74 non-RD patients. Clinical data were collected including clinical characteristics and laboratory tests. The RD group showed a higher proportion of females with a higher incidence of interstitial lung disease and kidney disease than the non-RD group. Also, the incidence of fatigue, olfactory dysfunction and musculoskeletal pain was higher in the RD group, but the incidence of cough, wheezing, and fever was lower compared with non-RD patients. The hospitalized course of the RD group (12.7 days ± 6.55) was significantly longer than that in the non-RD group (8.07 days ± 3.40). Also, patients in the RD group had higher levels of erythrocyte sedimentation rate, interleukin (IL)-2, and IL-4 than the non-RD group. The logistic regression analysis showed that dizziness and headache, C-reactive protein (CRP) > 8 mg/L and lactate dehydrogenase (LDH) > 248 μ/L were independent risk factors for severe COVID-19 infections of RD patients. RD patients who suffered from moderate or severe COVID-19 infections have a higher risk of comorbidities, higher levels of inflammation, and longer hospitalized course. Dizziness and headache, CRP > 8 mg/L and LDH > 248 μ/L are risk factors for severe COVID-19 infections in RD patients.


Prognostic significance of the location of intramural metastasis in patients with esophageal squamous cell carcinoma.
Although the presence of an intramural metastasis (IM) from esophageal cancer is associated with a poor prognosis, some patients with IM have a relatively favorable course. Clinicopathological factors including number, location, and size of IM and the distance between the primary tumor and IM were assessed in 212 patients with esophageal squamous cell carcinoma who underwent esophagectomy. Twenty-three patients (10.8%) had IM. IM size ranged from 2 to 100 mm (18+/-26), and the distance between primary lesion and IM ranged from 5 to 70 mm (27+/-18). Survival of ten patients with an IM less than 20 mm from the primary tumor was significantly longer than that of 13 patients with a more distant IM ( P=0.0184); median survival time were 2.3 and 0.7 years, respectively. A subgroup of patients with an IM less than 20 mm from the primary esophageal cancer may have a relatively favorable prognosis. When an IM is found preoperatively or in a resected specimen, measurement of the distance between the primary tumor and the IM might be useful in determination of treatment strategy and evaluation of prognosis.


Gastrointestinal cancer occurs as extramuscular manifestation in FSHD1 patients.
Facioscapulohumeral dystrophy type1 (FSHD1) patients with a shortened D4Z4 repeat containing the DUX4 gene have a broad spectrum of clinical manifestations. In addition, high expression of DUX4 protein with an aberrant C terminus is frequently identified in B cell acute lymphoblastic leukemia. We investigated clinical manifestations in 31 FSHD1 patients and 30 non-affected individuals. Gastrointestinal cancers (gastric and colorectal cancers) increased after the age of 40 years and were more frequently observed in FSHD1 patients (n = 10) than in non-affected individuals (n = 2, p = 0.0217), though the incidence of cancers occurring in non-gastrointestinal tissues of FSHD1 patients was the same as that of non-affected individuals (p > 0.999). These comorbidities of FSHD1 patients were not associated with D4Z4 repeat number. Our results suggest that gastrointestinal cancers are among the extramuscular manifestations of adult FSHD1 patients, and do not depend on D4Z4 repeat number.


Perception of frontal facial images compared with their mirror images: chirality, enantiomorphic discrimination, and relevance to clinical practice.
What we think we see consists of models constructed in our brains, which may be constrained, limited and perhaps modified at a cerebral level. Patients may view their mirror image differently to how others and the clinical team view them. Understanding potential variations in perception between real and mirror images is important in clinical practice. The aims were to assess differences in self-perception between frontal facial and mirrored photographs, comparing the results with selfie photographs. Facial photographs were taken by one investigator under standardized conditions for preclinical and clinical students. Each student took a selfie photograph at rest and smiling using his/her smartphone. A mirror image was generated for each image. Each student was shown his/her original and mirror image, without being informed which was which. For each pair of images, students were asked to choose which photograph they perceived as more attractive. A set of photographs of a male volunteer was shown to all participants, to choose either the original or mirror image as the more attractive. Most observers preferred the true image of the volunteer (P < 0.05), which may be evidence that most people prefer the true image of others, which is how they normally view them. Most observers preferred their own original photograph in frontal view at rest and smiling (P < 0.05), but preferred the mirror image of their selfie photograph at rest and smiling (P < 0.05). Significant differences in perceptions of attractiveness between true and mirror-reversed frontal and selfie images were found. Observers preferred their image the way they view themselves in a mirror. The selfie is how other people view an individual. If a selfie is flipped horizontally, that is how an individual sees themselves in a mirror. Most observers preferred the mirror image of their selfie, which is how they would view themselves in a mirror.


Autistic traits in children with ADHD index clinical and cognitive problems.
Traits of autistic spectrum disorders (ASD) occur frequently in attention deficit hyperactivity disorder (ADHD), but the significance of their presence in terms of phenotype and underlying neurobiology is not properly understood. This analysis aimed to determine whether higher levels of autistic traits, as measured by the Social Communication Questionnaire (SCQ), index a more severe presentation in a large, rigorously phenotyped sample of children with ADHD (N=711). Regression analyses were used to examine association of SCQ scores with core ADHD features, clinical comorbidities and cognitive and developmental features, with adjustment for putative confounders. For outcomes showing association with total SCQ score, secondary analyses determined levels of differential association of the three ASD sub-domains. Results suggest that increasing ASD symptomatology within ADHD is associated with a more severe phenotype in terms of oppositional, conduct and anxiety symptoms, lower full-scale IQ, working memory deficits and general motor problems. These associations persisted after accounting for ADHD severity, suggesting that autistic symptomatology independently indexes the severity of comorbid impairments in the context of ADHD. Sub-domain scores did not show unique contributions to most outcomes, except that social deficits were independently associated with oppositional symptoms and repetitive behaviours independently predicted hyperactive-impulsive symptoms and motor problems. It would be worthwhile for clinicians to consider levels of socio-communicative and repetitive traits in those with ADHD who do not meet diagnostic criteria for ASD, as they index higher levels of phenotypic complexity, which may have implications for efficacy of interventions.


The Identification of Anthocyanins from Padus racemosa and Its Protective Effects on H2 O2 -Induced INS-1 Cells Damage and STZ-Induced Diabetes Mice.
Oxidative damage in cells induced by reactive oxygen species (ROS) is a main factor in diabetes mellitus diseases progression. The composition of anthocyanins from Padus racemosa (APR) and the protective effects of APR on H2 O2 -induced rat insulinoma (INS-1) cells damage and streptozocin (STZ)-induced diabetes mice were investigated in this study. The main components of APR were cyanidin-cyanidin glucosyl-rutinoside, cyanidin-cyanidin xylosyl-rutinoside, cyanidin-xylosyl-glucoside and cyanidin-rutinoside, which were determined by liquid chromatography-mass spectrometry (LC/MS). APR could scavenge the 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radical and superoxide radical in vitro. ROS level was decreased and the cell viability was increased in INS-1 cells after treated with APR. Cell apoptosis induced by H2 O2 in INS-1 cells was decreased after incubation with APR. APR could decrease the phosphorylation of p38 and the nuclear translocation of p65, which indicated that APR could inhibit the activation of p38 Mitogen-activated protein kinase (MAPK) and Nuclear factor kappa B (NF-κB) cell signaling pathways. Meanwhile, APR could effectively reduce the blood glucose and blood lipid in STZ-induced diabetic mice. These results suggested that APR might be a potential agent for diabetes mellitus diseases treatment.


Assessing timewise changes over 15 months in life-space mobility among community-dwelling elderly persons.
The purpose of this study was to examine the differences of timewise changes in life-space mobility between elderly people living alone and those living with others among community-dwelling elderly people from a day care facility with a rehabilitation service for seniors. The present study used a longitudinal design with repeated measures every 3 months. In conformity with our inclusion criteria, this study included 233 community-dwelling elderly users of a day care facility with rehabilitation services for seniors in Japan. We analyzed the life-space assessment (LSA) scores collected at five time points (baseline, 3 months, 6 months, 9 months, and 12 months) using mixed-effects models with random intercepts and slopes over time. In the present study, the explanatory variables of interest were time, and living situation (living alone or with others). As possible confounders, we considered the following: (a) age, (b) sex, (c) social frailty, (d) physical frailty, (e) mild cognitive impairment (MCI), (f) depression, and (g) economic satisfaction. The mean age of participants was 78.9 years (SD = 7.7), their mean LSA score was 60.1 points (SD = 25.7), and 42.9% of the participants were men. After adjusting for age, gender, frailty, depression, MCI, and economic satisfaction, the mean LSA score of older adults who lived with others was significantly lower (7.42 points, 95%CI = - 18.30 to - 0.15, p = 0.048) than that older adults who lived alone. Community-dwelling older adults who used a day care center with rehabilitation services and lived with others had a smaller life-space at baseline than those who lived alone. This suggests that there is a need to pay more attention to social frailty among both older adults who live alone and those who live with others. According to a multilevel analysis growth model, elderly persons who lived with others had significantly lower life-space mobility than those who lived alone.


The activity of purified Bordetella pertussis components in murine encephalopathy.
A murine encephalopathic syndrome can be induced by the administration of BSA and whole-cell pertussis vaccine. The present paper reports studies of the capacity of purified individual pertussis components to induce this effect. Pertussis toxin and endotoxin together with a highly immunogenic sensitizer protein were required to induce the effect. The strength of the antibody response to the sensitizer appeared to be more important than the H-2 type of the recipient in determining the susceptibility of different mouse strains. The relevance of this syndrome to the study of possible vaccine-induced encephalopathy in man is uncertain and requires further investigation.


Risks and benefits of the skin-to-skin cesarean section - a retrospective cohort study.
Comparing maternal and neonatal outcomes after conventional cesarean section (CS) versus a "natural" or "skin-to-skin" cesarean section (SSCS). Retrospective cohort of women who underwent a SSCS (01-2013 until 12-2013) compared to conventional CS (08-2011 to 08-2012). CS before 37 weeks, under general anesthesia and in case of fetal distress were excluded. Main outcome measures were maternal blood loss, post-operative infection and admission; neonatal infection and admission; procedural outcomes. We analyzed 285 (44%) women in the SSCS-group and 365 (56%) in the conventional CS-group. There were no significant differences in surgical site infection (2.1% versus 1.6%; RR 1.1; 95%CI 0.64-2.0), or other maternal outcomes. Fewer neonates born after SSCS were admitted to the pediatric ward (9.5% versus 18%; RR 0.58; 95%CI 0.41-0.80) and fewer neonates had a suspected neonatal infection (2.0% versus 7.3%; RR 0.40; 95%CI 0.19-0.83). No differences were observed for other outcomes. Mean operation time was 4m42s longer in the SSCS-group compared to the conventional CS-group (58m versus 53m; 95%CI 2m44s-6m40s). Mean recovery time was 14m46s shorter (114m versus 129m; 95%CI 3m20s-26m). Adverse maternal and neonatal outcomes were not increased after skin-to-skin cesarean compared to conventional cesarean delivery.


The role of endothelial progenitor cells in tumour vasculogenesis.
To review the biological behaviour of endothelial progenitor cells and their role and significance in tumour vasculogenesis. The data in this review were mainly from Medline and PubMed for the relevant articles in English published from March, 1997, to March, 2008. The search terms were 'endothelial progenitor cells' (EPCs) and 'neoplasm'. Articles about the biological behaviour of EPCs and their roles in tumour vasculogenesis were included. EPCs, whose characteristics are similar to those of endothelial cells (ECs) and stem cells, contribute to tumour vasculogenesis during tumour progression. The mobilisation, recruitment, homing and incorporation of EPCs into tumours are multi-step and multi-factor events during tumour vasculogenesis. This complex process requires the participation of many growth factors and cells, such as tumour cells, ECs, stromal cells and EPCs in the tumour microenvironment. However, there is still some debate about EPC distribution, contribution, origin and differentiation in tumour vasculogenesis. The characterisation of tumour-associated EPCs may provide valuable clues for more specific anti-angiogenesis therapy and/or tumour diagnosis. Many challenges remain in understanding definition, differentiation, mobilisation and recruitment of EPCs.


Restoration of c-Src/Fyn Proteins Rescues Mitochondrial Dysfunction in Huntington's Disease.
Aims: Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder with no effective therapies. Mutant huntingtin protein (mHTT), the main HD proteinaceous hallmark, has been linked to reactive oxygen species (ROS) formation and mitochondrial dysfunction, among other pathological mechanisms. Importantly, Src-related kinases, c-Src and Fyn, are activated by ROS and regulate mitochondrial activity. However, c-Src/Fyn involvement in HD is largely unexplored. Thus, in this study, we aimed at exploring changes in Src/Fyn proteins in HD models and their role in defining altered mitochondrial function and dynamics and redox regulation. Results: We show, for the first time, that c-Src/Fyn phosphorylation/activation and proteins levels are decreased in several human and mouse HD models mainly due to autophagy degradation, concomitantly with mHtt-expressing cells showing enhanced TFEB-mediated autophagy induction and autophagy flux. c-Src/Fyn co-localization with mitochondria is also reduced. Importantly, the expression of constitutive active c-Src/Fyn to restore active Src kinase family (SKF) levels improves mitochondrial morphology and function, namely through improved mitochondrial transmembrane potential, mitochondrial basal respiration, and ATP production, but it did not affect mitophagy. In addition, constitutive active c-Src/Fyn expression diminishes the levels of reactive species in cells expressing mHTT. Innovation: This work supports a relevant role for c-Src/Fyn proteins in controlling mitochondrial function and redox regulation in HD, revealing a potential HD therapeutic target. Conclusion: c-Src/Fyn restoration in HD improves mitochondrial morphology and function, precluding the rise in oxidant species and cell death. Antioxid. Redox Signal. 38, 95-114.


The role of mechanotransduction versus hypoxia during simulated orthodontic compressive strain-an in vitro study of human periodontal ligament fibroblasts.
During orthodontic tooth movement (OTM) mechanical forces trigger pseudo-inflammatory, osteoclastogenic and remodelling processes in the periodontal ligament (PDL) that are mediated by PDL fibroblasts via the expression of various signalling molecules. Thus far, it is unknown whether these processes are mainly induced by mechanical cellular deformation (mechanotransduction) or by concomitant hypoxic conditions via the compression of periodontal blood vessels. Human primary PDL fibroblasts were randomly seeded in conventional six-well cell culture plates with O2-impermeable polystyrene membranes and in special plates with gas-permeable membranes (Lumox®, Sarstedt), enabling the experimental separation of mechanotransducive and hypoxic effects that occur concomitantly during OTM. To simulate physiological orthodontic compressive forces, PDL fibroblasts were stimulated mechanically at 2 g·cm-2 for 48 h after 24 h of pre-incubation. We quantified the cell viability by MTT assay, gene expression by quantitative real-time polymerase chain reaction (RT-qPCR) and protein expression by western blot/enzyme-linked immunosorbent assays (ELISA). In addition, PDL-fibroblast-mediated osteoclastogenesis (TRAP+ cells) was measured in a 72-h coculture with RAW264.7 cells. The expression of HIF-1α, COX-2, PGE2, VEGF, COL1A2, collagen and ALPL, and the RANKL/OPG ratios at the mRNA/protein levels during PDL-fibroblast-mediated osteoclastogenesis were significantly elevated by mechanical loading irrespective of the oxygen supply, whereas hypoxic conditions had no significant additional effects. The cellular-molecular mediation of OTM by PDL fibroblasts via the expression of various signalling molecules is expected to be predominantly controlled by the application of force (mechanotransduction), whereas hypoxic effects seem to play only a minor role. In the context of OTM, the hypoxic marker HIF-1α does not appear to be primarily stabilized by a reduced O2 supply but is rather stabilised mechanically.


COVID-19 pandemic and the consequential effect on patients with endometriosis.
What was the effect of the coronavirus disease 2019 (COVID-19) pandemic on healthcare and quality of life in those suffering from endometriosis? Our study reveals a clear correlation between the deterioration of the reported physical and mental state and impaired medical care for patients suffering from endometriosis during the COVID-19 pandemic. The quality of life of patients suffering from endometriosis is compromised in a variety of aspects. In response to the ongoing COVID-19 pandemic, self-isolation practices aimed at curbing the spread of COVID-19 have severely complicated the availability of proper medical care worldwide. The study involved a cross-sectional international self-reported online survey. Responses were accepted between November 2020 and January 2021. The survey was prepared by the Department of Obstetrics and Gynaecology in a medical university setting. The survey contained 17 questions and was placed online. Cooperation with different endometriosis organizations around the world enabled distribution of the survey through their social media platforms. The study participants (n = 3024 replies) originated from 59 countries. The questionnaire was created after a literature review and is partially based on the validated quality of life questionnaires, adjusted to the study question. The survey was then translated to 15 other languages following World Health Organization recommendations as closely as possible. Chi-square tests for independence were carried out for the analysis of the two variables: suspension of health services, and the patients mental and physical well-being. Out of 3024 participants from 59 countries who submitted the questionnaire between November 2020 and January 2021, 2964 (98.01%) provided information that enabled a full analysis. For the 1174 participants who had their medical appointments cancelled, 43.7% (n = 513) reported that their symptoms had been aggravated, and 49.3% (n = 579) reported that their mental state had worsened.In comparison, of the 1180 participants who kept their appointments, only 29.4% (n = 347) stated that their symptoms had been aggravated, and 27.5% (n = 325) stated their mental health had worsened. The results showed that there was a significant link between the reported deterioration of mental and physical wellbeing and impaired medical care (cancellation) (P ≪ 0.001). A total of 610 participants did not have medical appointments scheduled, and these participants followed a similar pattern as the participants who kept their appointments, with 29.0% (n = 177) reporting aggravation of symptoms and 28.2% (n = 172) reporting that their mental state had worsened. Cultural differences among international participants are to be expected and this may have affected how participants from different countries interpreted and answered the questionnaire. Translating the questionnaire into 15 different languages, even though incorporating backwards translation, could possibly lead to different interpretations of given questions, simply based on different wording in the languages. The majority of respondents (around 90%) were from Europe and South America and therefore the findings may not be generalizable to other locations. Further research is needed to assess the true impact and long-term consequences of the COVID-19 pandemic for patients living with endometriosis. This study received no funding and the authors declare they have no relevant conflicts of interest. N/A.


Surface expression and partial characterization of an arsonate hapten-specific idiotype-bearing T-cell receptor.
Anti-idiotype antibodies raised against the arsonate hapten idiotype have been used to detect arsonate-binding receptors on the surface of peripheral T cells of A/J mice and to isolate this material after biosynthetic labeling for partial chemical characterization. It was found that 2-3% of splenic T cells from arsonate-immune mice specifically bound the hapten using immunofluorescent keyhole limpet hemocyanin as a carrier. In double-immunofluorescence labeling experiments, a high proportion (approximately equal to 70%) of these cells also bound the (Fab')2 fragment of rabbit anti-idiotype antibody in exactly the same patches on the cell as the arsonate hemocyanin antigen. In addition, the anti-idiotype antibody inhibited the binding of the hapten-carrier complex to T cells by approximately equal to 70%. In parallel experiments, fowl antibodies against mouse (Fab')2 fragments bound to 100% of arsonate-binding T cells in the same cell-surface patches as the hapten, and were capable of inhibiting 100% of the hapten-binding cells. Capping, shedding, and resynthesis experiments indicated that the T cells synthesized their antigen-binding idiotype-bearing receptors. Immunoblots of unreduced detergent extracts of purified splenic T cells developed with anti-idiotype antibodies showed bands at 150,000 and 94,000 Da. Equal amounts of protein extracted from liver and analyzed in the same gels as the T-cell material failed to show any reactivity with anti-idiotype antibodies. To confirm the biosynthetic origin of the idiotype-positive materials, detergent extracts from 75Se-methionine- or [3H]leucine-labeled Con A-treated splenic T cells were reacted with anti-idiotype antibodies and the bound material was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the presence of 2-mercaptoethanol the major band was at 68,000 Da, with variable minor levels of material at 45,000 Da, while when hapten was used to isolate the receptor a dominant 25,000- to 30,000-Da band was seen. We believe that the higher-molecular-weight materials are multimers of the 25,000-30,000 subunit.


PARP1 and PRC2 double deficiency promotes BRCA-proficient breast cancer growth by modification of the tumor microenvironment.
Poly (ADP-ribose) polymerase 1 (PARP1) and polycomb-repressive complex 2 (PRC2) are each known for their individual roles in cancer, but their cooperative roles have only been studied in the DNA damage repair process in the context of BRCA-mutant cancers. Here, we show that simultaneous inhibition of PARP1 and PRC2 in the MDA-MB-231 BRCA-proficient triple-negative breast cancer (TNBC) cell line leads to a synthetic viability independent of the mechanisms of DNA damage repair. Specifically, we find that either genetic depletion or pharmacological inhibition of both PARP1 and PRC2 can accelerate tumor growth rate. We attribute this to modifications in the tumor microenvironment (TME) that are induced by double-depleted breast cancer cells, such as promoting intratumoral angiogenesis and increasing the proportion of tumor-promoting type 2 (M2) macrophages. These changes subsequently inhibit cell death and promote proliferation. Mechanistically, we find that PARP1 and PRC2 double depletion induces not only a basal activation of the NF-κB pathway but also a maximal activation of NF-κB within the TME in response to external stimuli such as hypoxia and the presence of macrophages. In summary, our study reveals an unprecedented synthetic viable interaction between PARP1 and PRC2 in BRCA-proficient TNBC and identifies NF-κB as the downstream mediator. DATABASE: RNA-seq data are available in the GEO databases under the accession GSE142769.


Endogenous opioid and cannabinoid systems contribute to antinociception produced by administration of NSAIDs into the insular cortex of rats.
Pain sensation is characterized as a complex experience, dependent on sensory processes as well as the activation of limbic brain areas involved in emotion, among them anterior insula. This cortical area is involved in the perception and response to painful stimuli. We investigated if this area contributes to antinociception produced by NSAIDs, and underlying mechanisms. We found that administration of NSAIDs into the anterior insular cortex in rats reduced mechanical and heat hyperalgesia produced by intraplantar injection of formalin, and this was attenuated by pre- or post-treatment with the opioid receptor antagonists, naloxone and CTOP, and the cannabinoid receptor (CB1) antagonist AM-251. These data support the concept that NSAID-evoked antinociception is mediated via descending endogenous opioid and cannabinoid systems inhibiting spinal paw withdrawal reflexes in rodents.


The Penn Classification System for Malperfusion in Acute Type A Dissection: A 25-Year Experience.
The University of Pennsylvania classification system (Penn class) of acute type A aortic dissection (aTAAD) is used to evaluate the impact of malperfusion on surgical outcomes. The purpose of this analysis was to determine the validity of Penn class in a larger and more contemporary cohort and to compare its performance with other classification systems. This was a retrospective study of patients who underwent aTAAD repair at our institution from 1993 to 2020. Patients were assigned to Penn class on the basis of burden of preoperative malperfusion syndrome. The association of Penn class and 30-day mortality was evaluated by multivariable regression. The discriminatory ability of Penn class for mortality was determined by a bootstrapped C statistic. There were 1192 patients, of whom 50% were assigned to Penn class A (no ischemia), 21% (253/1192) to class B (local ischemia), 14% (171/1192) to class C (generalized ischemia), and 14% (167/1192) to class B-C (combined ischemia). The incidence of mortality rose significantly with increasing Penn class from 5% (31/601) in class A to 35% (59/167) in class B-C (P < .001). After adjustment, 30-day mortality increased significantly with class B (odds ratio [OR], 2.43; 95% CI, 1.38-4.27), class C (OR, 3.39; 95% CI, 1.90-6.03), and class B-C (OR, 13.08; 95% CI, 7.90-22.15) compared with class A. The C statistic was 0.77 (95% CI, 0.72-0.80) and was significantly higher than for models featuring alternative classification systems (P < .05). Penn class provides excellent discrimination for 30-day mortality after repair of aTAAD.


Primary oat-cell carcinoma of the larynx.
A primary oat-cell carcinoma of the larynx in a 63-year-old man is reported. The oat-cell pattern appeared intermingled at one edge with a squamous carcinoma. The origin of this mixed tumour is considered together with the literature of extrapulmonary carcinomas having an oat-cell pattern.


A novel framework for horizontal and vertical data integration in cancer studies with application to survival time prediction models.
Recently high-throughput technologies have been massively used alongside clinical tests to study various types of cancer. Data generated in such large-scale studies are heterogeneous, of different types and formats. With lack of effective integration strategies novel models are necessary for efficient and operative data integration, where both clinical and molecular information can be effectively joined for storage, access and ease of use. Such models, combined with machine learning methods for accurate prediction of survival time in cancer studies, can yield novel insights into disease development and lead to precise personalized therapies. We developed an approach for intelligent data integration of two cancer datasets (breast cancer and neuroblastoma) - provided in the CAMDA 2018 'Cancer Data Integration Challenge', and compared models for prediction of survival time. We developed a novel semantic network-based data integration framework that utilizes NoSQL databases, where we combined clinical and expression profile data, using both raw data records and external knowledge sources. Utilizing the integrated data we introduced Tumor Integrated Clinical Feature (TICF) - a new feature for accurate prediction of patient survival time. Finally, we applied and validated several machine learning models for survival time prediction. We developed a framework for semantic integration of clinical and omics data that can borrow information across multiple cancer studies. By linking data with external domain knowledge sources our approach facilitates enrichment of the studied data by discovery of internal relations. The proposed and validated machine learning models for survival time prediction yielded accurate results. This article was reviewed by Eran Elhaik, Wenzhong Xiao and Carlos Loucera.


A Pilot Trial of Topical Capsaicin Cream for Treatment of Cannabinoid Hyperemesis Syndrome.
Patients with cannabinoid hyperemesis syndrome (CHS) present frequently to the emergency department. Previous case studies suggest dramatic symptomatic improvement with topical capsaicin treatment. This exploratory study examined the potential effectiveness of topical capsaicin in patients with nausea and vomiting due to a suspected CHS exacerbation. This was a double-blind, randomized placebo-controlled pilot trial. Adults who presented with vomiting suspected to be from CHS were eligible for enrollment. We excluded pregnant women and those with resolution of symptoms. Following randomization, topical 0.1% capsaicin or placebo cream was applied to the anterior abdomen in a uniform manner. The primary outcome was the severity of nausea on a visual analog scale (VAS) of 0 to 10 cm assessed at 30 minutes. Secondary outcomes were adverse events, occurrence of posttreatment vomiting, nausea by VAS at 60 minutes, and hospital admission. This pilot trial enrolled 30 patients, 17 in the capsaicin arm and 13 in the placebo arm. One patient in the capsaicin arm did not tolerate treatment due to skin irritation. Mean ± SD nausea severity at 30 minutes was 4.1 ± 2.3 cm in the capsaicin arm and 6.1 ± 3.3 cm in the placebo arm (difference = -2.0 cm, 95% confidence interval [CI] = 0.2 to -4.2 cm). At 60 minutes, mean ± SD nausea severity was 3.2 ± 3.2 cm versus 6.4 ± 2.8 cm (difference = -3.2 cm, 95% CI = -0.9 to -5.4 cm). The percent reduction in nausea at 60 minutes from baseline was 46.0% in the capsaicin arm and 24.9% in the placebo arm (difference = 21.1%, 95% CI = -5.6% to 47.9%). A higher proportion of capsaicin group patients (29.4% vs. 0%) had complete resolution of nausea (relative risk = 3.4, 95% CI = 1.6 to 7.1). In this pilot trial, the application of topical capsaicin cream was associated with a significant reduction in nausea at 60 minutes but not at 30 minutes and provided more complete relief of nausea.


Comparison of CEA and CA19-9 as a predictive factor for recurrence after curative gastrectomy in gastric cancer.
Our aim of was to compare importance of the tumor markers (TMs) serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in prediction of recurrence after curative gastrectomy for gastric cancer. We reviewed retrospectively the clinical records of 149 patients who underwent curative gastrectomy for stage I-III gastric cancer and whose CEA and CA19-9 levels were determined once preoperatively and for more than 3 years postoperatively. We investigated whether the clinicopathological characteristics of patients including age, sex, pathological disease stage, operative approach, type of gastrectomy, and degree of lymph node dissection as well as preoperative positivity of CEA and CA19-9 were risk factors for recurrence in univariate and multivariate analyses. Rate of recurrence was compared between patients positive and negative for postoperative CEA or CA19-9. We also calculated sensitivity, specificity, positive and negative predictable values of postoperative positivity of CEA and CA19-9 for recurrence. The lead time was compared between CEA and CA19-9 that was defined as the time of the first detection of increases in tumor markers and confirmation of recurrence on imaging modalities. The number of patients positive for preoperative CEA was 25 (17%) and for CA19-9 was 11 (7%). Recurrence was confirmed in 29 (19%) patients. Stage III disease, preoperative positivity for CA19-9 but not CEA, and total gastrectomy were risk factors for recurrence in univariate analysis, but stage III disease was the only risk factor for recurrence in multivariate analysis. Forty and 15 patients were positive for postoperative CEA and CA19-9, respectively. The recurrence rate of 47% (7/15) in patients positive for postoperative CA19-9 was greater than that in negative patients (22/134 = 16%), but it did not differ between patients who were positive or negative for postoperative CEA. Specificity for CA19-9 was greater than that for CEA (P < 0.05). The lead time of CEA (3.9 ± 4.7 months) was not different from that of CA19-9 (6.1 ± 7.1 months). These results indicate that CA19-9 rather than CEA is likely to be more useful for the detection of recurrence after curative gastrectomy for gastric cancer.


Anthroposophic medicine in the treatment of pediatric pseudocroup: A systematic review.
In Europe only few integrative pediatric wards exists and there are two German hospitals focusing on anthroposophic medicine as part of complementary and alternative medicine (CAM). Whilst the most common pediatric diseases are treated here, pseudocroup patients make up a large group in these hospitals, receiving conventional as well as anthroposophic therapies. However, effectiveness of these therapy concepts mostly based on physicians' experiences but clinical studies are hitherto missing. A systematic literature search identifying therapy approaches for pseudocroup in children was conducted in general electronic databases (Cochrane Library, PubMed, OVID) and in CAM-specific databases (CAMbase, CAM-QUEST®, Anthromedics). Search results were screened for anthroposophic therapy options. In addition, anthroposophic guidebooks were handsearched for relevant information. Among 157 articles fulfilling search criteria one retrospective study, and five experience reports describing anthroposophic treatments were identified. Several medications for the treatment of pseudocroup were mentioned such as Aconitum, Apis, Bryonia, Hepar sulfuris, Lavender, Pyrit, Sambucus and Spongia. During appropriate use no adverse effects were reported. Anthroposophic medicine harbors a broad spectrum of remedies for the treatment of pseudocroup in children. In particular, Aconitum, Bryonia and Spongia are frequently recommended; however, clinical trials investigating the effectiveness are sparse. Therefore, development and validation of therapy strategies are required.


Automated and Efficient Generation of General Molecular Aggregate Structures.
Modeling intermolecular interactions of complex non-covalent structures is important in many areas of chemistry. To facilitate the generation of reasonable dimer, oligomer, and general aggregate geometries, we introduce an automated computational interaction site screening (aISS) workflow. This easy-to-use tool combines a genetic algorithm employing the intermolecular force-field xTB-IFF for initial search steps with the general force-field GFN-FF and the semi-empirical GFN2-xTB method for geometry optimizations. Compared with the alternative CREST program, aISS yields similar results but with computer time savings of 1-3 orders of magnitude. This allows for the treatment of systems with thousands of atoms composed of elements up to radon, e.g., metal-organic complexes, or even polyhedra and zeolite cut-outs which were not accessible before. Moreover, aISS can identify reactive sites and provides options like site-directed (user-guided) screening.


Prediction of the Joint Toxicity of Multiple Engineered Nanoparticles: The Integration of Classic Mixture Models and In Silico Methods.
An approach to solve the emerging need of prediction of the toxicity of mixtures of engineered nanoparticles (ENPs) is presented. The integration of classic approaches to mixture toxicity assessment and computational toxicology approaches is proposed to be a smart strategy for forecasting the toxicity of a mixture of ENPs.


Extravasation and outcomes in computed tomography and angiography in patients with pelvic fractures requiring transcatheter arterial embolization: A single-center observational study.
Extravasation on contrast-enhanced computed tomography (CECT) is a helpful indicator of the need for transcatheter arterial embolization (TAE) for pelvic fractures. However, previous reports were inconsistent on cases in which angiography is necessary, even though there is no extravasation on computed tomography. This study aimed to describe and analyze the contradictory findings in cases where extravasation is observed on angiography but not on CECT, to contribute to improved management of patients with pelvic fractures. This was a retrospective single-center study. Patients with pelvic fractures who underwent CECT and TAE between 2014 and 2020 were included. We classified the patients into three groups: CECT and angiography with extravasation (CT+Angio+), CECT with no extravasation and angiography with extravasation (CT-Angio+), and CECT with extravasation and angiography without extravasation (CT+Angio-). A total of 113 patients were included in the study: the CT+Angio+ group had 54 patients, CT-Angio+ group, 47; and CT+Angio- group, 12. The CT-Angio+ group had a significantly longer time from arrival to CECT than the CT+Angio+ group (27 minutes vs. 23 minutes, p < 0.05). The CT-Angio+ group had significantly more blood transfusions (fresh frozen plasma, platelets) within 24 hours than the CT+Angio- group did (p < 0.05), and ventilator management days (p < 0.05) and intensive care unit stays (p < 0.05) were significantly longer. There was no significant difference in outcomes among the three groups. There was no difference in severity, transfusion volume, or mortality in patients with pelvic fractures needing TAE, classified as CT-Angio+, compared with that of CT+Angio+ patients. Even in the absence of extravasation in the pelvic region on CECT, angiography or TAE may still be necessary. Therapeutic/Care Management, Level IV.


Spider phylosymbiosis: divergence of widow spider species and their tissues' microbiomes.
Microbiomes can have profound impacts on host biology and evolution, but to date, remain vastly understudied in spiders despite their unique and diverse predatory adaptations. This study evaluates closely related species of spiders and their host-microbe relationships in the context of phylosymbiosis, an eco-evolutionary pattern where the microbial community profile parallels the phylogeny of closely related host species. Using 16S rRNA gene amplicon sequencing, we characterized the microbiomes of five species with known phylogenetic relationships from the family Theridiidae, including multiple closely related widow spiders (L. hesperus, L. mactans, L. geometricus, S. grossa, and P. tepidariorum). We compared whole animal and tissue-specific microbiomes (cephalothorax, fat bodies, venom glands, silk glands, and ovary) in the five species to better understand the relationship between spiders and their microbial symbionts. This showed a strong congruence of the microbiome beta-diversity of the whole spiders, cephalothorax, venom glands, and silk glands when compared to their host phylogeny. Our results support phylosymbiosis in these species and across their specialized tissues. The ovary tissue microbial dendrograms also parallel the widow phylogeny, suggesting vertical transfer of species-specific bacterial symbionts. By cross-validating with RNA sequencing data obtained from the venom glands, silk glands and ovaries of L. hesperus, L. geometricus, S. grossa, and P. tepidariorum we confirmed that several microbial symbionts of interest are viably active in the host. Together these results provide evidence that supports the importance of host-microbe interactions and the significant role microbial communities may play in the evolution and adaptation of their hosts.


Improvement in the specificity of the silver staining technique for AgNOR-associated acidic proteins in paraffin sections.
Some recently developed silver staining methods allow selective staining of acidic nucleolar proteins. Pretreating deparaffinized sections with Schiff's reagent improves the specificity of Goodpasture and Bloom's AgNOR staining (as modified by Kodama et al.) after aldehyde fixation.


Hyperchloraemic metabolic acidosis following open cardiac surgery.
To describe acid-base derangements in children following open cardiac surgery on cardiopulmonary bypass (CPB), using the Fencl-Stewart strong ion approach. Prospective observational study set in the paediatric intensive care unit (PICU) of a university children's hospital. Arterial blood gas parameters, serum electrolytes, strong ion difference, strong ion gap (SIG), and partitioned base excess (BE) were measured and calculated on admission to PICU. A total of 97 children, median age 57 months (range 0.03-166), median weight 14 kg (range 2.1-50), were studied. Median CPB time was 80 minutes (range 17-232). Predicted mortality was 2% and there was a single non-survivor. These children showed mild metabolic acidosis (median standard bicarbonate 20.1 mmol/l, BE -5.1 mEq/l) characterised by hyperchloraemia (median corrected Cl 113 mmol/l), and hypoalbuminaemia (median albumin 30 g/l), but no significant excess unmeasured anions or cations (median SIG 0.7 mEq/l). The major determinants of the net BE were the chloride and albumin components (chloride effect -4.8 mEq/l, albumin effect +3.4 mEq/l). Metabolic acidosis occurred in 72 children (74%) but was not associated with increased morbidity. Hyperchloraemia was a causative factor in 53 children (74%) with metabolic acidosis. Three (4%) hyperchloraemic children required adrenaline for inotropic support, compared to eight children (28%) without hyperchloraemia. Hypoalbuminaemia was associated with longer duration of inotropic support and PICU stay. In these children with low mortality following open cardiac surgery, hypoalbuminaemia and hyperchloraemia were the predominant acid-base abnormalities. Hyperchloraemia was associated with reduced requirement for adrenaline therapy. It is suggested that hyperchloraemic metabolic acidosis is a benign phenomenon that should not prompt escalation of haemodynamic support. By contrast, hypoalbuminaemia, an alkalinising force, was associated with prolonged requirement for intensive care.


Aggregation pheromones in 2 Australian hard ticks, Ixodes holocyclus and Aponomma concolor.
The presence of an aggregation pheromone has been demonstrated for the first time in indigenous Australian ticks. Filter paper discs exposed to either Australian paralysis ticks Ixodes holocyclus or echidna ticks Aponomma concolor showed inter-sex or intra-sex attraction for ticks of their own species. Nymphal exuviae of Ap, concolor were highly attractive to adult ticks. Discs were significantly attractive to I. holocyclus at distances up to 80 cm.


Syrian refugee child workers: Gender differences in ergonomic exposures and musculoskeletal health.
This study explores sex/gender-related differences in ergonomic exposures and musculoskeletal disorders for 4090 working Syrian refugee children (>8-≤18 years) in the Bekaa Valley, Lebanon (n = 2107 males; n = 1983 females). Data was collected on demographic, occupational, and socioeconomic indicators and musculoskeletal disorders. Results revealed that children engaged in strenuous work. Ergonomic exposures differed by sex/gender, with girls more likely to engage in repetitive movements and boys in heavy lifting. Girls bore a double burden of work inside and outside their households and were more prone to wrist and hand pain. More girls reported working under pressure to finish their job on time while more boys reported that their salary is based on finishing a specific number of items per day. Syrian refugee child workers need immediate protection to safeguard their health. Interventions could target children of legal age for work in safer conditions and keep younger children out of work.


A field evaluation of formalin-gasoline technique in the concentration of stool for detection of intestinal parasites.
A field evaluation of the formalin-gasoline procedure to detect parasite ova, cysts, or larvae from 470 fecal specimens (comprising both fresh and formalin-preserved stool samples) was compared with that of the formalin-ether sedimentation technique. Parallel concentrates with diethyl ether and gasoline were prepared for each specimen, and the species and appearance of recovered parasite species were determined. Of 470 total specimens, 206 (43.83%) were found to be positive for parasites in one or both concentration techniques. Gasoline was comparable to diethyl ether in the recovery of parasite eggs, cysts, and larvae, so that the formalin-gasoline and the formalin-diethyl ether sedimentation techniques detected 165 and 156 positive of total specimens, respectively. In this study, gasoline proved to be as good as diethyl ether in concentrating parasite eggs and cysts, as well as in maintaining characteristic morphology. However, gasoline was considerably superior to diethyl ether in detecting larvae of Strongyloides stercoralis. Parallel examination of total stool samples by the routine formalin-ether (original) and by the formalin-gasoline techniques resulted in identical distribution of positive slides and morphology of recovered parasite species. However, the easy availability of gasoline (wherever gas stations are present) and its low cost in comparison to ether makes gasoline superior to ether for use in concentration of stools by the sedimentation method in laboratories, including laboratories with limited material resources and also laboratories present in small cities and rural health centers.


In vivo reflectance confocal microscopy features of cutaneous microcirculation and epidermal and dermal changes in diffuse systemic sclerosis and correlation with histological and videocapillaroscopic findings.
Videocapillaroscopy of the nail fold is the current gold standard to assess progressive changes of the capillary network in patients with systemic sclerosis (SSc). Reflectance confocal microscopy (RCM) is a non-invasive optical imaging tool that allows in vivo visualization of the skin structures and cutaneous microcirculation. To investigate qualitative and quantitative changes of the cutaneous microcirculation and dermal-epidermal alterations of SSc patients by RCM and to correlate the images with findings of videocapillaroscopy and histology. Ten patients affected by diffuse-type SSc with skin involvement and 10 healthy controls were enrolled. All subjects underwent RCM of the dorsal and ventral surfaces of the middle third of the left forearm and nailfold videocapillaroscopy. Skin biopsies for histological and immunohistochemical investigations were taken from 5 patients and 2 healthy controls. At RCM observation, the diameter, perimeter and area of cutaneous capillaries were significantly increased in comparison to healthy controls, as histologically confirmed, whereas blood flow speed was significantly slower. Videocapillaroscopy showed a pathologic pattern of disease activity in 8 SSc patients and was non-specific in the remaining 2. In addition, RCM showed epidermal atrophy, flattening of rete ridges and dermal fibrosis in 7 SSc patients with long-standing disease but not in 3 patients with a recent onset. RCM provides measurable morphological and functional findings of microcirculation in patients suffering from diffuse-type SSc. These findings can integrate with, but not substitute, those provided by standard videocapillaroscopy. In addition, unlike videocapillaroscopy, RCM allows the investigation of epidermal and dermal changes.


Hospitalisations up to adulthood for children born with orofacial clefts.
The aim of this study was to compare hospital admissions from infancy to adulthood, between children born with orofacial clefts (OFC) and those without OFC. The method used was a cohort study using record-linked administrative datasets. Participants included all children liveborn in Western Australia (WA) between 1980 and 2010 diagnosed with OFC, who were frequency matched by year of birth to randomly selected liveborn children without OFC. We calculated rate ratios (RR) of hospital admission, number and reason of admissions, cumulative length of stay, for each cleft type (cleft lip only (CLO), cleft lip and palate (CL+P), cleft palate only (CPO), no OFC) and by age period (infancy, pre-school, primary and high school ages, and early adulthood). Overall, 1396 children were diagnosed with an OFC and compared with 6566 children without OFC. Individuals born with OFC were up to three times more likely to be admitted to hospital, had more admissions and longer cumulative length of stay in all age periods. Children with OFC were also more likely to be admitted for ear and digestive system conditions (RR up to 30 and six times higher, respectively). Children with CL+P and CPO were more likely to be admitted for respiratory conditions (RR 1.3-2.0) and children with CPO were six times more likely to be admitted for care for other congenital anomalies. Throughout childhood, individuals born with OFC were more likely to be admitted, and had more hospitalisations than those without OFC. Children born with CL+P or CPO had a higher hospitalisation burden than children born with CLO.


Regulation of the production of granulocyte-macrophage colony-stimulating factor by macrophage-like tumour cell lines.
Macrophage tumour cell lines (PU5-1.8, P388D1) produced detectable granulocyte macrophage colony-stimulating (CSF-2) activity measured using a factor-dependent cell line FDC-P1. The production of CSF-2 was enhanced by endotoxin and inhibited by serum, and correlated inversely with [3H]TdR incorporation. mRNA isolated from PU5-1.8 or P388D1 cells initiated CSF-2 production when injected into Xenopus laevis oocytes. The specific activity in this assay was unaltered in mRNA isolated from endotoxin-treated cells. The results suggest that endotoxin acts at a post-transcriptional level.


Adrenic acid non-enzymatic peroxidation products in biofluids of moderate preterm infants.
Oxidative stress plays an essential role in processes of signaling and damage to biomolecules during early perinatal life. Isoprostanoids and isofuranoids from the free radical-catalyzed peroxidation of polyunsaturated fatty acids (PUFAs) are widely recognized as reliable biomarkers of oxidative stress. However, their quantification is not straightforward due to high structural similarity of the compounds formed. In this work, a semiquantitative method for the analysis of adrenic acid (AdA, C22:4 n-6) non-enzymatic peroxidation products (i.e. dihomo-isoprostanes and dihomo-isofurans) was developed. The proposed ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method was applied to the analysis of blood plasma and urine from preterm infants providing information about AdA peroxidation.


Synergistic antitumor effect by coexpression of chemokine CCL21/SLC and costimulatory molecule LIGHT.
To establish a more efficient treatment for immunotherapy against solid tumors, we have evaluated the antitumor effect by coexpression of a chemokine CCL21/secondary lymphoid tissue chemokine and a costimulatory molecule LIGHT in colon carcinoma C26. C26 cells expressing either CCL21 or LIGHT exhibited a significantly reduced tumor growth in vivo, and mice inoculated with these cells showed a prolonged survival, but eventually all these mice died. In contrast, C26 cells expressing both CCL21 and LIGHT exhibited a minimal tumor growth in vivo, and all these mice survived healthily with a tumor remission and consequently acquired a strong protective immunity. A markedly increased infiltration of mature dendritic cells (DCs), and CD8(+) T cells was observed in the tumor mass, and their spleen cells showed a greatly enhanced cytotoxic T lymphocyte (CTL) activity against C26 tumor and interferon (IFN)-gamma production. Neutralization of IFN-gamma or depletion of CD8(+) or CD4(+) T cells significantly reduced the antitumor activity. These results suggest that the combined treatment with CCL21 and LIGHT is able to induce a synergistic antitumor effect to eradicate tumor completely by greatly enhancing tumor-infiltration of lymphocytes including mature DCs and CD8(+) T cells, resulting in markedly augmented CTL activity and IFN-gamma production.


Thermoregulatory model to predict physiological status from ambient environment and heart rate.
A real-time thermoregulatory model was developed for predicting real-time physiological responses of workers engaged in various tasks for prolonged time. The unique feature of the present model is primarily on metabolic activity inputs derived from minimum non-invasive measures (i.e., heart rate and ambient temperature). In addition, it utilizes individual anthropological characteristics (height, weight, and clothing) as an input to estimate core temperatures (T(c)). The model was validated using data from five laboratory studies (n=63) with varied environments, clothing, and heat acclimation status. Overall, T(c) predictions using this simplified model, corresponded well with measured values (root mean square deviation: 0.05-0.31 degrees C).


Optogenetic stimulation of basal forebrain cholinergic neurons prevents neuroinflammation and neuropsychiatric manifestations in pristane induced lupus mice.
Neuroinflammation has been identified as one of the primary pathogenic factors of neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no dedicated treatments available in clinics to alleviate neuroinflammation in NPSLE. It has been proposed that stimulating basal forebrain (BF) cholinergic neurons may provide potent anti-inflammatory effects in several inflammatory diseases, but its potential role in NPSLE remains unexplored. This study aims to investigate whether and how stimulating BF cholinergic neurons has a protective effect on NPSLE. Optogenetic stimulation of BF cholinergic neurons significantly ameliorated olfactory dysfunction and anxiety- and depression-like phenotype in pristane induced lupus (PIL) mice. The increased expression of adhesion molecules (P-selectin and vascular cell adhesion molecule-1 (VCAM-1)), leukocyte recruitment, blood-brain barrier (BBB) leakage were significantly decreased. Notably, the brain histopathological changes, including the elevated levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), IgG deposition in the choroid plexus and lateral ventricle wall and lipofuscin accumulation in the cortical and hippocampal neurons, were also significantly attenuated. Furthermore, we confirmed the colocalization between the BF cholinergic projections and the cerebral vessels, and the expression of α7-nicotinic acetylcholine receptor (α7nAChR) on the cerebral vessels. Our data indicate that stimulation of BF cholinergic neurons could play a neuroprotective role in the brain through its cholinergic anti-inflammatory effects on cerebral vessels. Therefore, this may be a promising preventive target for NPSLE.


Effectiveness of electrothermal bipolar vessel-sealing devices versus other electrothermal and ultrasonic devices for abdominal surgical hemostasis: a systematic review.
Adequate hemostatic techniques are essential for optimal intra- and postoperative results. A number of different hemostatic techniques and devices have been developed over the past few years, but which device should be preferred during laparoscopic and open abdominal procedures? We conducted a systematic search for randomized controlled trials (RCTs) that compared the effectiveness and costs of vessel-sealing devices with those of other electrothermal or ultrasonic devices in abdominal surgical procedures. Seven RCTs that included 554 patients met the inclusion criteria. Various procedures that used a vessel-sealing device (LigaSure™) (n = 264) were compared to ultrasonic devices (n = 139) and mono- (n = 20) or bipolar devices (n = 130). LigaSure was favored in two studies with respect to less blood loss, shorter operating time, and lower costs. However, no differences were observed in the other studies. Considering the relatively low number of complications, all hemostatic devices used may be considered relatively safe. None of the studies reported on quality of life or cost effectiveness. Vessel-sealing devices may be considered safe and their use may reduce costs due to reduced blood loss and shorter operating time in some abdominal surgical procedures compared to mono- or bipolar electrothermal devices. Wider-ranging RCTs of sufficient quality that assess (cost) effectiveness are required to make firm conclusions.


Effect of placement of occlusive membranes on root resorption and bone regeneration during healing of circumferential periodontal defects in dogs.
Previous studies indicate that root resorption is a frequent sequela to significant amounts of periodontal repair in animal models. A model was developed in labrador dogs to study periodontal wound healing in large circumferential defects in the absence of influence from the oral environment. A polytetrafluorethylene membrane of 1 micron pore size (GORE-TEX) was used to occlude cells from specific tissues from populating the healing dentin-connective tissue wound. 3 modalities were studied: (1) control, in which no membrane and therefore no cell occlusion was used, (2) flap occlusion, in which the internal surface of the flap was lined with the membrane preventing contribution of cells from the flap, (3) bone occlusion, in which the reduced alveolar bone was lined with the membrane preventing contribution from bone cells. Wound closure included total submergence of teeth and membranes. The membranes remained incorporated and no exposure of membranes or teeth occurred during the 3 months healing period. Histology revealed bone regrowth in all 3 treatment modalities. It is suggested that inductive elements in the connective tissue or dentin, or bone cells from periosteum were responsible for bone regrowth in the bone membrane treatment modality. No significant difference was seen for root resorption between the 3 treatment modalities. This study found that physical occlusion of cells from the inside of the surgical flap, or from the pre-existing bone, is not sufficient to prevent root resorption in periodontal wound healing.


Single-shot ultrafast tomographic imaging by spectral multiplexing.
Computed tomography has profoundly impacted science, medicine and technology by using projection measurements scanned over multiple angles to permit cross-sectional imaging of an object. The application of computed tomography to moving or dynamically varying objects, however, has been limited by the temporal resolution of the technique, which is set by the time required to complete the scan. For objects that vary on ultrafast timescales, traditional scanning methods are not an option. Here we present a non-scanning method capable of resolving structure on femtosecond timescales by using spectral multiplexing of a single laser beam to perform tomographic imaging over a continuous range of angles simultaneously. We use this technique to demonstrate the first single-shot ultrafast computed tomography reconstructions and obtain previously inaccessible structure and position information for laser-induced plasma filaments. This development enables real-time tomographic imaging for ultrafast science, and offers a potential solution to the challenging problem of imaging through scattering surfaces.


Multivessel peripheral revascularization for acute stroke intervention: successful M2 bifurcation stenting and the growing case for comprehensive endovascular interventional training.
A comprehensive endovascular skill set is desirable and key to successful intervention in the patient with complex cardiovascular disease. Acute stroke intervention is the next frontier for the endovascular specialist. We report a case of acute stroke intervention in a patient with severe peripheral vascular disease performed by interventional cardiologists with peripheral endovascular skills that clearly demonstrates the new paradigm of global revascularization.


Clinical and immunologic evaluation of tyrosine-adsorbed Dermatophagoides pteronyssinus extract: a double-blind placebo-controlled trial.
We evaluated the clinical efficacy and immunologic changes associated with the administration of tyrosine-adsorbed Dermatophagoides pteronyssinus (Dpt) extract. The study was carried out in a double-blind, placebo-controlled fashion in 18 patients with Dpt-induced asthma during a trial period of at least 12 mo. Patients initially received six increasing doses once a week; the top dose of 400 Noon units was repeated at monthly intervals. Clinical response was on the basis of diary cards on which symptoms and medication scores were recorded; daily lung function measurements were made by use of a mini Wright's peak flow meter. The entire spectrum of physiologic measurements, medications, and symptoms were taken into account by computing daily scores over a 2-week period. Total IgE, Dpt-specific IgE antibodies, and leukocyte histamine release were measured before treatment and during hyposensitization. Changes in Dpt-specific IgG were evaluated with a double antibody antigen-binding assay by use of the purified fraction of mite extract F4P1. All patients had measurable levels of IgG antibodies to F4P1 before treatment. Treatment with tyrosine-adsorbed Dpt extract resulted in a significant increase of specific-IgG antibodies in the treated group at 2 and 6 mo only (nonparametric rank sum test). Variations relative to the pretreatment values of total and specific IgE were not significantly different in the treated and in the control patients after 2.6 and 12 mo. No significant decrease in leukocyte sensitivity was observed after treatment. It was only possible to demonstrate a significant diminution in the mean medication score (nonparametric sign test) in the first 6 mo for the treated group; independently of the beginning of the treatment, the treated group demonstrated a reduction of the mean medication score and an improvement in peak expiratory flow rate lung function before the midsummer months when seasonal increase in mite density can occur. Particular attention was paid to the methodological problems raised during this study and inherent in a trial in house dust-mite asthma.


Considering management behaviours to identify vulnerable caregivers of persons with dementia.
Persons with dementia gradually disengage from daily activities, and therefore require increasing daily support. Caregivers face a dilemma as to whether they should encourage the persons with dementia in terms of initiative and autonomy, or supervise and take charge of tasks, which may cause distress for both parties. This study seeks to better understand how caregivers manage the disengagement of the persons with dementia and the repercussions on their caregiving experience. A total of 217 caregivers participated. Their management behaviours and the characteristics of their caregiving experiences were assessed with questionnaires. A cluster analysis was first performed to identify possible profiles of management behaviours and comparison, which were then compared to identify the caregiving experience associated with each profile. The first cluster (25.8% of the sample) corresponds to caregivers with high negative control behaviour scores and high positive stimulation behaviour scores; the second cluster (43.8% of the sample) corresponds to caregivers with low positive stimulation behaviour scores and high negative control behaviour scores; and the third cluster (30.4% of the sample) corresponds to caregivers with low negative control behaviour scores and high positive stimulation behaviour scores. Caregivers in Clusters 2 and 3 differ in terms of anxiety, depression, burden, gratification, health and financial problems. Cluster 1 is an intermediate profile with similar characteristics to Cluster 3. Our results support the idea of considering management behaviours to identify vulnerable caregivers and highlight the deleterious role of negative control behaviours, especially when they are not offset by positive protective stimulation behaviours.


Therapeutic Applications of Mesenchymal Stem Cells: A Comprehensive Review.
Mesenchymal Stem Cells (MSCs) are one of the most promising tools for cell therapy, that are isolated from bone marrow and many other adult tissues such as liver, cord blood, placenta, dental pulp and adipose tissue. Due to the lack of MHC class II expression on the surface of MSCs, they can also be used as a potent cell source for tissue regeneration in non-autologous cell therapy applications. Many advantages of MSCs such as their self-renewal, in vitro proliferation, rapid cell doubling capacity, anti-fibrotic, anti-apoptotic, anti-inflammatory, immunomodulatory and immunosuppressive effects, and also paracrine nature have been demonstrated in various pre-- clinical studies and clinical evidence. The ability of MSCs to differentiate into multiple cell lineages, as well as the lack of ethical issues in comparison with embryonic and induced Pluripotent Stem Cells (iPSCs), has introduced them as a suitable candidate for cell therapy. This review provides a comprehensive overview of various clinical trials based on MSCs for the treatment of a variety of diseases, demonstrating their capability in the treatment of dermatological, musculoskeletal, neurological, cardiovascular, respiratory, renal, gastroenterological and urological conditions, etc.


Ryanodine in mammalian heart ventricular muscle: indication for the induction of calcium leakage from the sarcoplasmic reticulum.
Ryanodine at nanomolar concentrations suppressed the earlier of two contraction components which can be produced in guinea-pig papillary muscles, in the presence of noradrenaline (3 microM) at a low contraction frequency (0.2 Hz). However, test contractions elicited shortly after a steady state contraction showed an unimpaired early contraction component. This component declined with increases in the interval preceding the test contraction at a rate depending on the ryanodine concentration (the apparent first-order rate constant 0.07 s-1 of the spontaneous decline was doubled by about 0.2 nM and was increased to 1.3 s-1 by 10 nM ryanodine). The effect of ryanodine resembled that of a potassium-induced depolarization with the exception that it was not antagonized by an increase in the extracellular magnesium concentration. It is concluded that ryanodine enhances the leakage of stored calcium in mammalian heart muscle, probably by a direct influence on the calcium release channels of the junctional sarcoplasmic reticulum of the heart muscle cell.


Women's utilisation of quality antenatal care, intrapartum care and postnatal care services in Ethiopia: a population-based study using the demographic and health survey data.
This study sought to investigate the level and determinants of receiving quality antenatal care (ANC), intrapartum care, and postnatal care (PNC) services by women in Ethiopia. The quality of care a woman receives during ANC, intrapartum care, and PNC services affects the health of the woman and her child and her likelihood of seeking care in the future. Data from the nationally representative Ethiopia Mini Demographic and Health Survey 2019 were analysed for 5,527 mothers who gave birth within five years preceding the survey. We defined quality ANC as having: blood pressure measurement, urine and blood tests, informed of danger signs, iron supplementation, and nutritional counselling during ANC services; quality intrapartum care as having: a health facility birth, skilled birth assistance, and a newborn put to the breast within one hour of birth during intrapartum care services; and quality PNC as having: PNC within two days; cord examination; temperature measurement, and counselling on danger signs and breastfeeding of the newborn; and healthcare provider's observation of breastfeeding during PNC services. We used multilevel mixed-effects logistic regression analyses specifying three-level models: a woman/household, a cluster, and an administrative region to determine predictors of each care quality. The analyses employed sampling weights and were adjusted for sampling design. Thirty-six percent (n = 1,048), 43% (n = 1,485), and 21% (n = 374) women received quality ANC, intrapartum care and PNC services, respectively. Private healthcare facilities provided higher-quality ANC and PNC but poor-quality intrapartum care, compared to public health facilities. Having four or more ANC visits, commencing ANC during the first trimester, and higher women's education levels and household wealth indices were positive predictors of quality ANC use. Government health posts were less likely to provide quality ANC. Wealthier, urban-residing women with education and four or more ANC contacts were more likely to receive quality intrapartum care. Women who received quality ANC and skilled birth assistance were more likely to receive quality PNC. Teenage mothers were more likely to receive quality intrapartum care, but were less likely to receive quality PNC than mothers aged 20-49. We recommend standardizing the contents of ANC provided in all healthcare facilities; and promoting early and four or more ANC contacts, effectiveness, sensitivity and vigilance of care provided to teenage mothers, and women's education and economic empowerment.


A very brief note on why bacterial evolution has physiology.
The majority of bacteria live and evolve in surface biofilms. Both growth in biofilms and horizontal transfer of DNA are regulated by quorum-sensing pheromone signals. The common regulation of bacterial surface growth and DNA transfers illustrates how physiology contributes to bacterial evolution.


Treatment of breakthrough cancer pain: to titrate or to proportionate?
Breakthrough cancer pain can be treated effectively by rapid-onset opioids, such as sublingual fentanyl. However, it remained unclear how the optimal dose of sublingual fentanyl should be determined. Dosing proportional to basic opioid regimen is now proposed as an alternative to dose titration.


High body fat percentage is associated with primary aldosteronism: a cross-sectional study.
Excess aldosterone has been shown to be associated with obesity; however, there is currently a lack of data regarding the relationship between percentage of body fat and primary aldosteronism (PA), particularly pertaining to Asian populations. Furthermore, essential hypertension may mimic the condition of PA and there needs to be differentiation between the two. This study aimed to assess the association between percentage of body fat and PA. A cross-sectional study was conducted in the outpatient department of the Endocrine and Metabolism Unit of the tertiary care medical center in Thailand. Data was obtained from 79 patients who had been screened for PA due to hypertension in young-onset, hypokalemia, adrenal incidentaloma or resistance hypertension. Essential hypertension was defined as patients who had high blood pressure and were negative for PA screening. Body fat percentage was assessed by bioelectrical impedance analysis. The relationship between percentage of body fat and a diagnosis of PA was assessed using logistic regression analysis, including adjustment for confounding factors. The participants were divided into a PA group (n = 41) and an essential hypertension group (n = 38). After controlling for confounding variables (age, sex, body mass index, cholesterol and insulin resistance status), the odds ratio of having PA in males with a percentage of body fat > 25% and females with percentage > 30% was 1.82 (95%CI = 1.79-1.86, p < 0.001). A higher percentage of body fat is associated with an increased risk of PA. Further studies need to be conducted to confirm the relationship between body fat percentage and PA.


Monte Carlo simulations.
A description of Monte Carlo methods for simulation of proteins is given. Advantages and disadvantages of the Monte Carlo approach are presented. The theoretical basis for calculating equilibrium properties of biological molecules by the Monte Carlo method is presented. Some of the standard and some of the more recent ways of performing Monte Carlo on proteins are presented. A discussion of the estimation of errors in properties calculated by Monte Carlo is given.


cDNA clones completing the nucleotide and derived amino acid sequence of the alpha 1 chain of basement membrane (type IV) collagen from mouse.
Six cDNA clones add 3549 nucleotides to the DNA sequence of the alpha 1 chain of basement membrane (type IV) collagen. Thus the complete nucleotide and derived amino acid sequence of the alpha 1 type IV collagen with 5007 nucleotides coding for 1669 amino acids with a calculated Mr of 160,827 is known. The six cDNA clones cover the putative N-terminal signal peptide, the 7 S region and two thirds of the helical region extending into the previously published murine nucleotide sequence [(1986) Gene 43, 301]. The protein sequence for 289 amino acids of the helical region adjacent to the 7 S region has not previously been published for any species.


P-glycoprotein and its inhibition in tumors by phytochemicals derived from Chinese herbs.
P-glycoprotein belongs to the family of ATP-binding cassette (ABC) transporters. It functions in cellular detoxification, pumping a wide range of xenobiotic compounds, including anticancer drugs out of the cell. In cancerous cells, P-glycoprotein confers resistance to a broad spectrum of anticancer agents, a phenomenon termed multidrug resistance. An attractive strategy for overcoming multidrug resistance is to block the transport function of P-glycoprotein and thus increase intracellular concentrations of anticancer drugs to lethal levels. Efforts to identify P-glycoprotein inhibitors have led to numerous candidates, none of which have passed clinical trials with cancer patients due to their high toxicity. The search for naturally inhibitory products from traditional Chinese medicine may be more promising because natural products are frequently less toxic than chemically synthesized substances. In this review, we give an overview of molecular and clinical aspects of P-glycoprotein and multidrug resistance in the context of cancer as well as Chinese herbs and phytochemicals showing inhibitory activity towards P-glycoprotein.


A qualitative assessment of rheumatoid hand surgery in various regions of the world.
Differences in opinion between rheumatologists and hand surgeons result in disparate practice patterns among different states in the United States regarding the use of surgery for hand deformities in the rheumatoid population. The purpose of this project was to study the practices of rheumatoid hand surgery from countries in various regions of the world.


Cryosurgical ablation of atrioventricular junction without extracorporeal circulation.
A closed technique, using thoracotomy without cardiopulmonary bypass and atriotomy, for cryosurgical ablation of the atrioventricular node-His bundle junction is described. The technique was used in 34 patients selected from among 136 patients with disabling supraventricular tachyarrhythmias refractory to drug therapy in whom atrioventricular block was produced. After thoracotomy, four methods can be used to determine the site of cryoinstrument application: palpation of the internal anatomic landmarks, a "mechanical test," use of a cryoprobe, or recording of the His bundle electrogram. The cryoprocedure lasts 160 to 180 seconds at temperatures of -60 degrees to -80 degrees C and is repeated once or twice. Complete atrioventricular block was induced in 29 of the 34 patients. Paroxysmal tachycardia was terminated in 31. There were no operative deaths. The frequency of surgical complications was nearly three times lower than in the group of 77 patients subjected to open cryodestruction of the atrioventricular junction, and the length of hospital stay after the operation was an average of 4.7 days shorter. The follow-up for up to 6.5 years (mean 34 months) failed to show postoperative paroxysmal tachycardia or tachyarrhythmia in 31 patients. In my opinion, this rather safe method for ablation of the atrioventricular junction could be more widely used, especially if there are contraindications for extracorporeal circulation or if transvenous catheter ablation has failed.


Clinical Use of Tailored Computed Tomography to Prevent Poststernotomy Dehiscence.
Morphological and tissue density analysis of the sternum can be performed in the preoperative computed tomography (CT). The purpose of this study was to analyze morphology and tissue density of sternum in CT and effect for comparison sternal instability. Patients with sternal instability (n = 61) and sternal stability (n = 66) were enrolled in this study. All of the patients were studied using same thorax CT procedure. All the measurements were performed by one specific cardiovascular radiologist. The Hounsfield units (HUs) were measured in axial sections of the sternum trabecular bone. Sternal instability group mean HU was 75.36 ± 13.19 and sternal stability group HU was 90.24 ± 12.16 (p < 0.000). HU is the statically significant predictor of sternal instability. Our study showed a significant correlation between the mean HU value of sternum and sternal instability. We think that it is important to evaluate the existing thorax CT while performing preoperative risk analysis for sternal dehiscence.


Sulfur from biogas desulfurization: Fate of S during storage in manure and after application to plants.
Residues from hydrogen sulfide (H2S) removal in biogas filters contain sulfur (S) in various forms (sulfate, sulfide, elemental S) that, if properly stored, is potentially valuable as crop fertilizer. We investigated 1) the turnover of the S compounds from filter materials during storage in untreated and digested cattle manure (CM), and 2) the S fertilizer replacement value (SFRV) of the filter materials applied in pure form or mixed manure with and without storage. The S filter materials from four H2S removal processes (biological and physical-chemical) containing mostly sulfate and/or elemental S were added to untreated CM or digested CM and stored at 10 °C for six months. Afterwards, a pot experiment was established to assess the S availability in an oil-seed rape (Brassica napus) crop. Microbial reduction of sulfate into sulfide took place rapidly after 69 days storage of untreated CM. A lower reduction rate was observed in digested CM mixtures. After six months, 68% and 32% of the initial sulfate content were still present in mixtures containing the S filter materials from biological desulfurization with digested CM and untreated CM, respectively. Sulfate reduction was inhibited for 120 days when digested CM was mixed with S saturated solution from an ash filter, probably due to high pH (≥8.2) and redox potential (>-100 mV) levels. Oppositely, elemental S was immediately and simultaneously both reduced and oxidized. Relatively low losses of total S were observed during the present storage conditions. Despite S turnover, the SFRV of CM and digested CM significantly increased from 15-19% (of total S applied) to 56-90% when S filter materials were added. The storage of S filter materials in digested manure reduced the risk of sulfide production and potential S volatilization. The S filter materials were a valuable source of plant-available S.


The electrophysiological effects of nicotine in the rat cerebellum: evidence for direct postsynaptic actions.
The agonistic actions of nicotine in the cerebellum were dependent on the type of cerebellar neuron studied. Purkinje cells were inhibited and cerebellar interneurons were excited by pressure-ejected nicotine. The simultaneous iontophoresis of Mg2+ failed to block nicotine agonistic actions on either cell type. Since Mg2+ reduces presynaptic release of neurotransmitters, our findings suggest that the pharmacological actions of nicotine on cerebellar neurons are due to direct postsynaptic mechanisms.


A systematic review of the ability of urine concentration to distinguish antipsychotic- from psychosis-induced hyponatremia.
Life-threatening hyponatremia in psychotic patients is common and typically is attributable to either antipsychotic medication or to acute psychosis in those with the polydipsia-hyponatremia syndrome. The preferred treatment for one situation may worsen the hyponatremia if caused by the other situation. Hence it is critical to distinguish between these two possibilities. Case reports and series were identified through electronic databases. Fifty-four cases of hyponatremia without recognized causes in psychotic patients were divided into those with dilute (<plasma osmolality) or concentrated (>plasma osmolality) urine. The distribution of urine concentration and measures likely to be associated with psychotic illness and its treatment were compared in both groups. Naranjo׳s scale was utilized to determine the probability hyponatremia was drug-induced. Urine osmolality fit a bimodal distribution (intersection 219mOsm/kg) better than a unimodal distribution. 'Probable' drug-induced cases occurred 6.8 (95%CI=1.6-28.9) times more often in those with concentrated urine. Acute psychotic exacerbations occurred 4.5 (95%CI=0.4-54.1) times more often in those with dilute urine. These findings, as well as several other trends in the data, indicate that measures of urine concentration can help distinguish between antipsychotic-induced and psychosis-induced hyponatremia.


Osmotically induced tissue expansion with hydrogels: a new dimension in tissue expansion? A preliminary report.
The possibility of using an osmotically-driven system for effective tissue expansion has been verified. As a biocompatible and efficient system, a copolymer of methylmethacrylate and vinylpyrrolidone is used in animal research (rats). This hydrogel was able to generate, in vitro, a physical swelling pressure of approximately 235 mm Hg. The range of possible volume expansion in solutions of differing concentrations was 3 to 30 times its water-free gel form. In animal experiments a high biocompatibility and efficiency in tissue expansion can be observed.


Hypertension and Cognitive Health Among Older Adults in India.
To assess the prevalence of diagnosed and undiagnosed hypertension and their relationship to cognitive function in older adults in India. Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD), an in-depth national study of late-life cognition and dementia. Geriatric hospitals and respondents' homes across 14 states in India. N = 2,874 individuals aged 60 years and older from LASI-DAD. Hypertension was identified by self-report of physician diagnosis or measured blood pressure (BP) of 140/90 mmHg or higher. Undiagnosed hypertension was defined as hypertensive BP measurements, but no physician diagnosis. Controlled hypertension was defined as BP lower than 140/90 mmHg among those with a physician diagnosis. Total hypertension included both diagnosed and undiagnosed hypertension. A summary cognition score, derived from the sum of 18 cognitive tests administered in the LASI-DAD (range = 0-360) was used to assess cognitive function. Total hypertension prevalence was 63.2% (41.5% diagnosed and 21.6% undiagnosed). Among those with hypertension, 34.5% were undiagnosed, 34.2% were diagnosed but uncontrolled, and 31.3% were diagnosed and controlled. Neither diagnosed nor undiagnosed hypertension was related to cognitive function in fully adjusted models. Older age, female sex, less education, being widowed, rural residence, residing in the north or central regions, being in a scheduled caste or tribe, low consumption, being underweight, and history of stroke were all independently associated with worse cognitive test performance. Two-thirds of older Indian adults had hypertension, with the majority being undiagnosed or diagnosed but not adequately controlled. Hypertension was not independently associated with cognitive function, whereas sociodemographic factors were independently related to cognitive function. J Am Geriatr Soc 68:S29-S35, 2020.


Synthesis of 5'-functionalized nucleosides: S-Adenosylhomocysteine analogues with the carbon-5' and sulfur atoms replaced by a vinyl or halovinyl unit.
Adenosine and uridine analogues functionalized with alkenyl or fluoroalkenyl chain at C5' were prepared employing cross-metathesis, Negishi couplings, and Wittig reactions. Metathesis of the protected 5'-deoxy-5'-methyleneadenosine or uridine analogues with six-carbon amino acids (homoallylglycines) in the presence of Grubbs catalysts gave nucleoside analogues with the C5'-C6' double bond. Alternatively, the Pd-catalyzed cross-coupling between the protected 5'-deoxy-5'-(iodomethylene) nucleosides and suitable alkylzinc bromides also provided analogues with alkenyl unit. Stereoselective Pd-catalyzed monoalkylation of 5'-(bromofluoromethylene)-5'-deoxyadenosine with alkylzinc bromides afforded adenosylhomocysteine analogues with a 6'-(fluoro)vinyl motif. The vinylic adenine nucleosides produced time-dependent inactivation of the S-adenosyl-l-homocysteine hydrolases.


An unusually cold active nitroreductase for prodrug activations.
A set of PCR primers based on the genome sequence were used to clone a gene encoding a hypothetical nitroreductases (named as Ssap-NtrB) from uropathogenic staphylococcus, Staphylococcus saprophyticus strain ATCC 15305, an oxygen insensitive flavoenzyme. Activity studies of the translation product revealed that the nitroreductase catalyses two electron reduction of a nitroaromatic drug of nitrofurazone (NFZ), cancer prodrugs of CB1954 and SN23862 at optimum temperature of 20 °C together with retaining its maximum activity considerably at 3 °C. The required electrons for such reduction could be supplied by either NADH or NADPH with a small preference for the latter. The gene was engineered for heterologous expression in Escherichia coli, and conditions were found in which the enzyme was produced in a mostly soluble form. The recombinant enzyme was purified to homogeneity and physical, spectral and catalytical properties were determined. The findings lead us to propose that Ssap-NtrB represents a novel nitro reductase with an unusual cold active property, which has not been described previously for prodrug activating enzymes of nitroreductases.


Anion inhibition profiles of α-, β- and γ-carbonic anhydrases from the pathogenic bacterium Vibrio cholerae.
Among the numerous metalloenzymes known to date, carbonic anhydrase (CA, EC 188.8.131.52) was the first zinc containing one, being discovered decades ago. CA is a hydro-lyase, which catalyzes the following hydration-dehydration reaction: CO2+H2O⇋HCO3(-)+H(+). Several CA classes are presently known, including the α-, β-, γ-, δ-, ζ- and η-CAs. In prokaryotes, the existence of genes encoding CAs from at least three classes (α-, β- and γ-class) suggests that these enzymes play a key role in the physiology of these organisms. In many bacteria CAs are essential for the life cycle of microbes and their inhibition leads to growth impairment or growth defects of the pathogen. CAs thus started to be investigated in detail in bacteria, fungi and protozoa with the aim to identify antiinfectives with a novel mechanism of action. Here, we investigated the catalytic activity, biochemical properties and anion inhibition profiles of the three CAs from the bacterial pathogen Vibrio cholera, VchCA, VchCAβ and VchCAγ. The three enzymes are efficient catalysts for CO2 hydration, with kcat values ranging between (3.4-8.23)×10(5)s(-1) and kcat/KM of (4.1-7.0)×10(7)M(-1)s(-1). A set of inorganic anions and small molecules was investigated for inhibition of these enzymes. The most potent VchCAγ inhibitors were N,N-diethyldithiocarbamate, sulfamate, sulfamide, phenylboronic acid and phenylarsonic acid, with KI values ranging between 44 and 91μM.


A novel genotyping method for rapid identification of the Le gene to select patients for diagnosis with CA19-9.
The antigenic determinant of CA19-9 is synthesized by the α1,3/4fucosyltransferase encoded by the Le gene in the Lewis blood group system. Accordingly, a diagnosis with CA19-9 is not appropriate forLe-negative patients who possess the Le gene-mutated le alleles homozygously. A Le gene-specific PCR was undertaken to determine c59T>G by using a set of tag-sense and biotin-labeled anti-sense primers and a peptide nucleic acid-le-clamp which bound to G59 in the le alleles. Following mixing with streptavidin-coatedbluelatex beads, the PCR products were developed on a strip on which the complementary tag oligonucleotide to theLe gene-specific amplicon was immobilized. When the PCR products were developed on the strip, a clear line was rapidly observed in Le-positive but not in Le-negative individuals. In contrast, a significant number of cancer patients with Lewis-negative phenotype were found to possess CA19-9, while they were specifically genotyped asLe/-. No contradictory results were observed in cancer patients (n = 315) with respect to their Lewis genotypes and CA19-9 levels. c59T>G occurred commonly in the le alleles could be specifically and rapidly identified by the present method. This method appeared to be relevant forselecting cancer patientsto bediagnosed with CA19-9.