The Association Between Post-Traumatic Stress and Depressive Symptoms Among Older Puerto Ricans in Boston: How Does Loneliness Matter?
To examine the association between post-traumatic stress and depression and whether such an association differs by level of loneliness among older Puerto Ricans. Data were collected from 304 Puerto Ricans aged 60 and above living in the Greater Boston area who responded to questionnaires. We used ordinary least squares regression to examine the association between post-traumatic stress, loneliness, and depressive symptoms. Post-traumatic stress was significantly associated with higher levels of depression. The association between post-traumatic stress and depression was stronger for those experiencing a higher degree of loneliness. In working with older Puerto Ricans experiencing post-traumatic stress, it is important for mental health professionals to incorporate the assessment of loneliness and to prevent and reduce comorbid depression by addressing loneliness through improving social skills, enhancing social support, and reducing maladaptive social cognition.


OX40 signaling in head and neck squamous cell carcinoma: Overcoming immunosuppression in the tumor microenvironment.
OX40 is a member of the tumor necrosis factor (TNF) receptor family and a potent co-stimulatory pathway that when triggered can enhance T-cell memory, proliferation and anti-tumor activity in patients with metastatic cancer. Ongoing investigations at our institution have demonstrated that OX40 expressing T cells are found in abundance in the tumors of patients with advanced stage head and neck squamous cell carcinoma (HNSCC). This has led to the initiation of human clinical trials investigating OX40-directed therapy for patients with HNSCC in both the metastatic and curative setting. The purpose of this review is to explore what is known about OX40 signaling and discuss how this pathway potentially can be modulated to improve outcome for patients with HNSCC.


Upper esophageal sphincter augmentation reduces pharyngeal reflux in nasogastric tube-fed patients.
Aspiration of gastric refluxate is one of the most commonly observed complications among long-term nasogastric tube (NGT) fed patients. The upper esophageal sphincter (UES) pressure barrier is the main defense mechanism against pharyngeal reflux of gastric contents. Our objective was to investigate the efficacy and safety of the UES assist device (UES-AD) in preventing gastric reflux through the UES in long-term NGT-fed patients. Self-Controlled Case series. We studied 10 patients (mean age = 90.6 ± 3.4 years, four females) with dysphagia caused by stroke or dementia who were fed for 0.5 to 5 years (median = 3 years) by NGT. External pressures of 20 to 30 mm Hg were applied by using a handmade UES-AD, which was started 2 hours after the beginning of NGT infusion and was alternated between periods of 2 hours on and 2 hours off, for a total of 12 hours. Placement of the impedance sensors within the UES was guided by high-resolution manometry. Trans-UES and intraesophageal reflux events were recorded by using 24-hour combined pH-impedance measurements. No aspiration pneumonia events were noted in the period 1 month before or during the study in any of the cohort. Baseline UES pressure averaged 17.5 ± 9.4 mm Hg and was increased to 38.9 ± 11.9mm Hg after application of the UES-AD. Overall frequency of trans-UES reflux decreased significantly with the UES-AD compared to without (0.8 ± 0.9 vs. 3.3 ± 2.8, P < .05 for the 12-hour study period). There was no effect of the UES-AD on esophageal reflux events (7.4 ± 4.4 vs. 6.4 ± 3.0, P > .05). UES-AD significantly decreases the number of trans-UES reflux events and can potentially reduce the aspiration risk associated with NGT feeding. 4. Laryngoscope, 128:1310-1315, 2018.


Quantifying the relationship of HIV infection with clinicopathological spectrum and outcome among patients with colorectal cancer in a South African population.
Literature is limited on HIV and colorectal cancer (CRC) in sub-Saharan Africa despite it being the epicentre of the HIV epidemic. To compare clinicopathological features and outcome of CRC in HIV-negative and HIV-positive patients. Retrospective analysis of a prospective CRC database. Demographic details, HIV status, anatomical site, disease stage, treatment and follow-up were documented. Of 715 patients with CRC, 145 and 570 tested positive and negative respectively for HIV. Median age was 45 (IQR 36-53 and 57 (IQR 45-66) years among HIV-positive and HIV-negative patients respectively (p<0.0001). Tumour differentiation differed between the two groups (p=0.003) but staging was not different (p=0.6). Surgical resection rate was 52% for HIV-positive patients versus 59% for HIV-negative patients (p=0.07). Median follow-up was 9 (IQR 2-20.5) months for HIV-positive patients and 12 (IQR 6-29) months for HIV-negative patients (p=0.154). Recurrence rate was 14.7% among HIV positive patients and 6.8% in HIV negative patients (p=0.089). When compared with HIV-negative patients, HIV-positive patients with CRC presented at a younger age and tended to have lower surgical resection rates. There was no difference between the two groups with CRC in terms of anatomical sub-site distribution, disease staging and recurrence rates.


The effect of a touch-typing program on keyboarding skills of higher education students with and without learning disabilities.
This study examined the effect of a touch-typing instructional program on keyboarding skills of higher education students. One group included students with developmental learning disabilities (LD, n=44), consisting of students with reading and/or handwriting difficulties. The second group included normally achieving students (NA, n=30). The main goal of the program was to increase keyboarding speed while maintaining accuracy. The program included 14 bi-weekly touch-typing lessons, using the "Easy-Fingers" software (Weigelt Marom & Weintraub, 2010a), that combines a touch-typing instructional program and a keystroke logging program, to document the time and accuracy of each typed key. The effect of the program was examined by comparing keyboarding skills between the beginning (pre-test), the end of the program (post-test) and 3 months after termination of the program (long-term). Results showed that at the end of the program, keyboarding speed of the NA students decreased while the speed of the students with LD somewhat increased. In the long-term evaluation, both groups significantly improved their speed compared to pre-test. In both cases high accuracy (above 95%) was maintained. These results suggest that touch-typing instruction may benefit students in general, and more specific, students with LD studying in higher education, which often use computers in order to circumvent their handwriting difficulties.


A fluoroscopic imaging-guided computational analyses to inform internal tissue loads within fat pad of the diabetic foot during gait.
To accurately predict internal tissue loads for early diagnostics of diabetic foot ulcerations, a novel data-driven computational analysis was conducted. A dedicated dual fluoroscopic system was combined with a pressure mat to simultaneously characterize foot motions and soft tissue's material properties during gait. Finite element (FE) models of the heel pad of a diabetic patient were constructed with 3D trajectories of the calcaneus applied as boundary conditions to simulate gait events. The tensile and compressive stresses occurring in the plantar tissue were computed. Predictions of the layered tissue FE model with anatomically-accurate heel pad structures (i.e., fat and skin) were compared with those of the traditional lumped tissue (i.e., homogeneous) models. The influence of different material properties (patient-specific versus generic) on internal tissue stresses was also investigated. The results showed the peak tensile stresses in the layered tissue model were predominantly found in the skin and distributed towards the circumferential regions of the heel, while peak compressive stresses in the fat tissue-bone interface were up to 51.4% lower than those seen in the lumped models. Performing FE analyses at four different phases of walking revealed that ignorance of layered tissue structures resulted in an unphysiological increase of peak-to-peak value of stress fluctuation in the fat and skin tissue components. Thus, to produce more clinical-relevant predictions, foot FE models are suggested to include layered tissue structures of the plantar tissue for an improved estimation of internal stresses in the diabetic foot in gait.


Establishment and characterization of a human ovarian small cell carcinoma, hypercalcemic type, cell line (OS-1) secreting PTH, PthrP and ACTH--special reference to the susceptibility of anti-cancer drugs.
We successfully established a novel cell line (OS-1) derived from human ovarian small cell carcinoma, hypercalcemic type secreted PTH, PTH-rP and ACTH. The OS-1 cell line was established from metastatic focus of uterus. A patient was 25-year-old Japanese woman. The first she received left ovariectomy on April 2002. The histopathological diagnosis was ovarian small cell carcinoma, pT2c, Nx, Mx. Then on June 2003, metastatic focus of uterus was ectomied. A part of the recurrent tumor of uterus was cut into small pieces with razor blades, and dissociated with 0.1% trypsin-0.02% EDTA/ PBS(-) solution at room temperature. The single cells and small cell clusters were seeded into 60mm dishes and cultured in growth medium (GM: DMEM/F12 supplemented with 20% fetal bovine serum and 0.1% non-essential amino acids solution) at 37 degrees C, 4.7% CO2 in humidified air. Medium was exchanged twice a week. The OS-1 cells grew as floating cultures in the dishes. Radioimmunoassay of the conditioned media was revealed that the cultures secreted large amount of PTH, PTHrP and ACTH simultaneously. Susceptibilities of anti-cancer drugs to the OS-1 cells were examined using oxygen electrode meter (Daikin), and the results suggested VLB and TXL were effective, and CDDP, CPT-11, VP-16, VCR, CPA, MMC and CBDCA were not effective. In our knowledge, it is the first report that the cell line secreting PTH, PTHrP and ACTH was successfully established from ovarian small cell carcinoma, hypercalcemic type. We expect that OS-1 cell line contribute to study on the mechanism of ectopic hormone secretion and susceptibility of anti cancer drugs to the small cell carcinoma.


Photoinitiated synthesis of polymer brush from dendritic photoinitiator electrostatic self-assembly.
We report on a simple and effective method to prepare polymer brush by electrostatic self-assembly of dendritic macrophotoinitiator and photoinitiated polymerization.


Predictors of testicular viability in testicular torsion.
Testicular torsion (TT) requires prompt diagnosis and treatment to avoid testicular loss. Most studies have focused on the ideal work up to rule TT out in cases of acute scrotum. We attempted here to define objective criteria to select between orchidopexy and orchidectomy in patients undergoing surgery for TT. Fifteen boys with a median age at presentation of 7.8 (range 6.4-12) years undergoing surgical treatment for TT underwent color-Doppler ultrasound (CDU) preoperatively, and a bleeding test intraoperatively. Duration of preoperative history, degree of torsion, CDU findings and degree of bleeding were analyzed. Salvageability was independent of the degree of torsion. In patients with a history longer than 10h, no flow on CDU and no bleeding, after orchidectomy all the testicles were necrotic on pathology. When all these variables were negative, all the testicles did well during follow up. In the group of patients with no agreement among the analyzed variables, the outcome was unpredictable. Five out of six underwent orchidopexy, but in two cases the testicle atrophied (in spite of flow on CDU in one). No predictive parameters were found for testicular salvageability. Taken as a whole, the parameters studied can be of help in treatment choice. In patients with no agreement among the parameters, orchidopexy seems the appropriate option, but parents should be informed of the risk of testicular atrophy during follow up.


Cholinergic enzymes in neocortex, hippocampus and basal forebrain of non-neurological and senile dementia of Alzheimer-type patients.
Choline acetyltransferase (ChAT) activity and acetylcholinesterase (AChE) staining were examined in different cortical regions, hippocampal formation and basal forebrain of non-neurological controls and of patients afflicted with senile dementia of Alzheimer type (SDAT). Both enzymes showed a clear topographical distribution in the various regions studied. In SDAT cases, ChAT activity was reduced by 0-60% in the neocortex and by up to 97% in the hippocampus depending on the area and layer examined. In the nucleus of the diagonal band of Broca (NDB) and the medial septal nucleus (MSN), the activity was decreased by 65% and 55%, respectively; no significant change was found in the lateral septal nucleus (LSN), nucleus basalis of Meynert (NBM), substantia innominata (SI) and globus pallidus (GP). Comparable changes were seen in AChE staining. The results indicate that degeneration or dysfunction of cholinergic neurons in the medial septal area and possibly neocortex is an important characteristic of SDAT.


High-performance agarose gel chromatography in octyl glucoside of integral membrane proteins from human red cells, with special reference to the glucose transporter.
Integral membrane proteins and lipids from human red cells were fractionated in the presence of octyl glucoside by high-performance gel chromatography on a 22-ml column of the small-bead cross-linked agarose gel Superose 6, at 5 degrees C, pH 7.6 and 30-50 mM detergent. To avoid aggregation a relatively high flow-rate, 9 ml/h, was chosen. At low ionic strength four main fractions were resolved, which contained anion transporter multimers(I), glycophorin oligomers(II), glucose transporter dimers(III) and phospholipids(IV). In 0.5 M sodium chloride the resolution was lower but the yield of the glucose transporter was markedly higher, and chromatography of partially purified glucose transporter gave a protein recovery of about 90%. The apparent Mr values for the octyl glucoside complexes of the main components were: anion transporter, 900,000; glycophorin A, 210,000-360,000, dependent on ionic strength; glucose transporter, 110,000-160,000; lipids, 70,000. Some components aggregated with time: at a flow-rate of 1 ml/h mainly glycophorins and the glucose transporter were eluted, but no anion transporter, and fractionation performed 20 h after solubilization showed extensive aggregation of proteins. Superose-6 chromatography of glucose transporter and membrane lipids that had been isolated on DEAE-cellulose partially resolved the transporter and the phospholipid fractions. In this case, the resolution was better with 50 than with 30 mM detergent. The maximum glucose transport activity was approximately one-tenth of that observed before fractionation and appeared in two main fractions, at the main transporter fraction as well as at the overlap between the transporter and the lipids. The activity level was the same in both fractions, although the protein concentration was much lower in the second one. Addition of 2 mM egg-yolk phospholipids to the eluent did not increase the activity. This strongly indicates that the glucose transporter needs some specific membrane lipids to retain high transport activity. At the concentration of ca. 0.3 mg/ml used, the glucose transporter was probably eluted as a dimer in the absence of phospholipids and as a monomer in their presence.


Antimicrobial Efficacy of Cinnamon Essential Oil against Avian Pathogenic Escherichia coli from Poultry.
Colibacillosis, caused by E. coli, is responsible for economic losses in the poultry industry due to mortality, decreased production, and the cost of antibiotic treatments. Prevention of colibacillosis is based on improved biosecurity measures and the use of the vaccine performed with O78 E. coli strains, which is responsible for most cases of colibacillosis. Recently, there has been increased interest in other infection control methods, such as the use of natural compounds. The aim of this study was to evaluate the antimicrobial efficacy of cinnamon essential oil (CEO) against E. coli strains isolated from poultry. The MIC50 and MIC90 of CEO were determined by testing 117 strains belonging to serogroups O78, O2, O128, O139, isolated from laying hens (91 strains), broilers (10 strains), and turkeys (16 strains). The bacterial strains were tested at cell densities of 108 and 106 CFU/mL. At the cell density of 108 CFU/mL, MIC50 and MIC90 were 0.4 and 0.5 µL/mL for most of the tested strains, while they corresponded to 0.5 µL/mL for all strains isolated from broilers and for strains belonging to serogroup O139. At the cell density of 106 CFU/mL, MIC50 and MIC90 were 0.3 and 0.4 µL/mL, regardless of bird species of origin and for strains belonging to serogroups O78 and O2. In addition, a concentration of 0.04 µL/mL of CEO corresponded both to MIC50 and MIC90 for strains belonging to serogroups O139 and O128. Based on these results, cinnamon essential oil showed an effective antibacterial activity against E. coli strains from poultry and could find field application for the prevention of colibacillosis.


An Algorithm of l 1-Norm and l 0-Norm Regularization Algorithm for CT Image Reconstruction from Limited Projection.
The l 1-norm regularization has attracted attention for image reconstruction in computed tomography. The l 0-norm of the gradients of an image provides a measure of the sparsity of gradients of the image. In this paper, we present a new combined l 1-norm and l 0-norm regularization model for image reconstruction from limited projection data in computed tomography. We also propose an algorithm in the algebraic framework to solve the optimization effectively using the nonmonotone alternating direction algorithm with hard thresholding method. Numerical experiments indicate that this new algorithm makes much improvement by involving l 0-norm regularization.


[From the (un)freedom of embodied age(ing) in modern society and the necessity of a critical gerontological perspective of the body].
Perspectives on the aging body as a social construct and in its function as constructing the social are hitherto less developed in (social) gerontology. Nevertheless, "age(ing) and body" contains much more than biological changes and losses. In the body as a social medium and result of actions, we can understand the classical question connecting social structures and individual subjectivity in its social-structural and individual differentiation.The interrelationship between the body and other dimensions of the life situation is more than health; it also concerns employment, social contacts and material situation. The social construction of reality can be examined through the body especially in terms of the special way of function in the modern society (e.g. as experience society and consumer society). They include structural contradictions which can be recognised by individual ambivalences, expressed as, e.g., physical age(ing) in a youth-centred culture. In this article the main topic is to raise awareness in (critical) gerontology about the body as a social phenomenon.


Analysis of cholesterol ester accumulation in macrophages by the use of digital imaging fluorescence microscopy.
Low density lipoprotein (LDL) induced accumulation of cholesterol esters was analyzed by the digital imaging fluorescence microscopy (DIFM) in murine tumor macrophages. To analyze cholesterol ester accumulation, P388D1 macrophages were incubated with increasing quantities of unmodified or acetylated human LDL, washed, and live stained with a lipophylic fluorescent dye Nile Red. The increase in fluorescence intensity was quantitatively determined by the interactive laser cytometer (ACAS 470) and compared with the accumulation of cellular cholesterol esters determined by the gas liquid chromatography. Correlation between the two methods was highly significant (r greater than 0.9, P less than 0.001). A good agreement between the two methods was also found in terms of sensitivity and reproducibility. With the use of 589 nm narrowband interference filter in the light path of emitted light the intensity of fluorescence correlated well with cellular cholesterol ester content even in the presence of relatively high concentrations of triglycerides. Therefore, digital imaging fluorescence microscopy appears to be a reliable method for quantification of cholesterol ester accumulation at the single cell level offering new possibilities of studying interactions between cells and cholesterol ester rich lipoproteins.


How fast do very small abdominal aortic aneurysms grow?
Fifty patients with abdominal aortic aneurysms from 2.5 to 5.0 cm in anteroposterior diameter (median 3.1 cm, mean +/- S.E. 3.3 +/- 0.1 cm) were initially offered non-operative treatment. Two patients have subsequently undergone successful elective aneurysm resection because of increase in aneurysm size, and a third has died. The median annual growth rate of the aneurysm has been 0.22 cm and 77.8% increased in size between 6 monthly ultrasound examination. For aneurysms less than 4.0 cm the maximum 6 monthly increment in diameter was 0.7 cm. Even the smallest abdominal aortic aneurysms usually progressively increase in size and 6 monthly ultrasound remeasurement of aneurysm diameter is an essential component of non-operative management.


Financing needs to achieve Nationally Determined Contributions under the Paris Agreement in Caribbean Small Island Developing States.
Caribbean Small Island Developing States (SIDS) are highly vulnerable to the impacts of climate change. Given high mitigation and adaptation costs and constrained domestic finances, they seek international funding to meet their climate objectives. This paper investigates Caribbean SIDS perspectives on the role of international climate finance in addressing climate change and its effectiveness in meeting climate goals. The paper first explored the climate financing needs of sixteen Caribbean SIDS through a content analysis of their Nationally Determined Contributions (NDCs). It then compares the climate finance needs of the region with international climate finance commitments received by examining climate finance trends using data from the Organization for Economic Cooperation and Development (OECD) Development Assistance Committee's (DAC) Creditor Reporting System (CRS). The study revealed large gaps in estimating the climate finance needs of the region, as well as important patterns in the way climate finance is being distributed across mitigation, adaptation and overlap activity; principal versus significant climate objective; recipient country; sector; and source and type of funding. These findings are useful to help countries make decisions about how international climate finance should be used, and how its impacts should be evaluated and a basis for climate finance negotiations and dialogue with bilateral development partners and multilateral climate funds, and to assess whether available funds are being put to good use and identify problems that need to be addressed.


5-Lipoxygenase in mouse cerebellar Purkinje cells.
It has been suggested that the enzymatic pathway of 5-lipoxygenase (5-LOX) influences brain functioning and pathobiology. The mRNAs for both the enzyme 5-LOX and its activating protein FLAP have been found in the cerebellum. In this work, we investigated the cellular expression of 5-LOX in the adult mouse cerebellar cortex. We used the in situ mRNA hybridization assay, immunocytochemistry, laser capture microdissection, and our previously developed method for assaying the DNA methylation status of a putative mouse 5-LOX promoter. Since both 5-LOX mRNA in situ hybridization signal and FLAP immunoreactivity co-localize with calbindin 28 kD immunoreactivity (a Purkinje cell marker) but not with S-100β immunoreactivity (a Bergmann glia marker), the suggestion is that the 5-LOX pathway is expressed in cerebellar Purkinje cells. We found that methylation in the sites targeted by methylation-sensitive restriction endonucleases AciI and HinP1I but not BstUI and HpaII was greater in DNA samples obtained from a high-5-LOX-expressing cerebellar region (Purkinje cells) versus a low-5-LOX-expressing region (the molecular cell layer), suggesting a possible epigenetic contribution to the cell-specific 5-LOX expression in the cerebellum. We propose that Purkinje cell-localized 5-LOX and FLAP expression may be involved in the cerebellar synthesis of leukotrienes and/or could influence the Dicer-mediated microRNA formation and processes of neuroplasticity.


Accumulation of indium-111-labeled granulocytes in malignant tumors.
In a retrospective study of 220 [111In]granulocyte scintigrams from 208 patients, 25 patients had malignant neoplasms. Among these, tumor uptake of 111In activity was observed in ten patients (intense activity in two patients with non-Hodgkin's lymphoma and colonic carcinoma, respectively; moderate uptake in a patient with non-Hodgkin's lymphoma, and in a patient with an ovarian carcinoma; weak activity in three patients with cerebral neoplasms; and activity within otherwise "cold" metastatic lesions of the liver in three patients). Microscopic investigation following specific granulocyte staining revealed the greatest extent of granulocyte infiltration in the tumors which took up 111In activity, emphasizing the importance of tumor granulocyte infiltration as the single most important factor underlying tumor accumulation of 111In activity during [111In]granulocyte scintigraphy.


Pollution status of heavy metals and metalloids in Chinese lakes: Distribution, bioaccumulation and risk assessment.
Due to intensive human activities, most of Chinese lakes are suffering from the pollution of heavy metals and metalloids. Previous studies on heavy metals and metalloids in Chinese lakes were limited to a few lakes and mainly focused on sediments, to date the knowledge on heavy metals and metalloids in multiple media of Chinese lakes from a national perspective is scarce. We collected the data of nine heavy metals and metalloids including Copper (Cu), Cadmium (Cd), Lead (Pb), Mercury (Hg), Arsenic (As), Chromium (Cr), Nickel (Ni), Zinc (Zn), and Manganese (Mn) in water, surface sediments, and fish of 87 Chinese lakes sampled in the period from 2009 to 2019 from the literature, summarized the distribution of heavy metals and metalloids, evaluated their pollution, and apportioned their sources from a national perspective. Concentration of individual heavy metal and metalloid in water, surface sediments, and fish in Chinese lakes was in the ranges of 0.0080-282 μg/L, 0.020-33858 μg/g, and 0.00030-207 μg/g, respectively. 5.6 % and 33.3 % of lake water were polluted by Cd and As. 88.2 %, 78.6 %, and 66 % of lake sediments were polluted by Cd, Hg, and As. 35.3 %, 11.3 %, 52.4 %, and 12.8 % of Cd, Pb, As, and Cr concentrations in lake fish exceeded the food limits. Concentrations of heavy metals and metalloids in fish viscera were higher than those in other organs. Higher partition coefficient and bioaccumulation factors were found for Pb and Cd, Hg and Zn, respectively. Concentrations of heavy metals and metalloids in both water and sediments of lakes in eastern China were higher than those in western China. Concentrations of heavy metals and metalloids in both lake water and sediments of urban lakes were higher than those of rural lakes. Lakes with extremely high ecological risk of heavy metals and metalloids were mainly located in central China and eastern China. Pollution of heavy metals and metalloids in Chinese lakes was closely correlated with regional economic development. Heavy metals and metalloids in Chinese lakes were mainly derived from industrial, domestic, and mixed discharges. Cd and Hg were selected as the heavy metals for priority control in Chinese lakes.


Familial papillary thyroid carcinoma.
Over the last decade, several lines of evidence have been accumulated that support the existence of fPTC susceptibility genes. Preliminary clinical characteristics of fPTC have been identified, and linkage studies have identified the chromosomal locations of putative fPTC susceptibility genes. A logical clinical approach to fPTC is emerging.


An improved method for elimination of mycoplasmas from cell cultures.
Cell lines infected by different species of mycoplasma (Mycoplasma orale, Mycoplasma hominis) were decontaminated by co-culture with human blood monocyte (BM)-derived macrophages and pooled human immunoglobulin preparations. Co-cultures with BM-derived macrophages or murine peritoneal macrophages (PM) alone were not successful. The phenotype of infected cell lines did not differ from that of uninfected cell lines as revealed by morphological, enzymecytochemical, and immunocytochemical analysis.


Muscle involvement in the cerebro-oculo-facio-skeletal syndrome.
We report a 14-year-old male, born to consanguineous parents, with microcephaly, intracranial calcification, severe mental retardation, cataracts, optic atrophy, pigmentary retinopathy, contractures, scoliosis, and failure to thrive. His brain imaging revealed extensive basal ganglia calcifications. He has normal ultraviolet sensitivity. These features are consistent with the autosomal recessive cerebro-oculo-facio-skeletal syndrome. In addition, he has severe muscle weakness with end-stage muscle changes on biopsy. There have been few reports of muscle involvement in cerebro-oculo-facio-skeletal syndrome, and this is the first time it has been described in a cerebro-oculo-facio-skeletal patient with normal ultraviolet sensitivity. This case extends the extensive phenotypic similarities between cerebro-oculo-facio-skeletal syndrome patients with and without abnormal ultraviolet sensitivity, and highlights the cerebro-oculo-facio-skeletal syndrome in the differential diagnosis of congenital muscular dystrophies.


Risk factors and foetal growth restriction associated with expectant treatment of early-onset preeclampsia.
To identify the factors affecting expectant management of early-onset preeclampsia, and evaluate the correlation between expectant treatment and foetal growth restriction. The retrospective study included 72 women who were admitted for early-onset preeclampsia between February 2018 to April 2021. Data included maternal clinical parameters, demographic and maternal and neonatal outcomes, which were analysed for correlation. Multiple logistic regression analysis demonstrated that the time interval from the onset of 24-h proteinuria to termination of pregnancy showed a strong correlation with the expectant treatment; Univariate logistic analysis confirmed that there was no correlation between expectant treatment and foetal growth restriction. There was a negative correlation between the duration of 24-h proteinuria and the expectant treatment of patients with early-onset preeclampsia; Expectant treatment could not improve the development of foetal growth restriction in patients with early-onset preeclampsia.KEY MESSAGESThe duration of 24-h proteinuria affects the effectiveness of expectant management of early-onset preeclampsia.Expectant management can reduce adverse neonatal outcomes due to iatrogenic preterm delivery, but it cannot improve the occurrence of foetal growth restriction.


Melanotropin structure-activity studies on melanocytes of the teleost fish, Synbranchus marmoratus.
The minimal sequence of alpha-MSH required for full agonism on fish (Synbranchus marmoratus) melanocytes was determined to be Ac-alpha-MSH5-10-NH2 since Ac-alpha-MSH6-10-NH2 and Ac-alpha-MSH6-9-NH2 were inactive. The N-terminal tripeptide sequence, Ser-Tyr-Ser, lacked any contribution to potency since the 4-13 (Ac-[Nle4]-alpha-MSH4-13-NH2) sequence was equipotent to alpha-MSH. The important potentiating amino acids were found to be Met at position 4 of the amino terminus and Val at position 13 of the carboxy terminus of the hormone, since Ac-alpha-MSH4-10-NH2 was about 100 times more potent than the Ac-alpha-MSH5-10-NH2 sequence, and Ac-[Nle4]-alpha-MSH4-13-NH2 was about 10 times more active than Ac-[Nle4]-alpha-MSH4-12-NH2. The minimal sequence for equipotency to alpha-MSH was demonstrated to be Ac-[Nle4]-alpha-MSH4-13-NH2. [Nle4, D-Phe7]-alpha-MSH was about 10 times more active than alpha-MSH. Unexpectingly, several conformationally restricted cyclic melanotropins were either partial agonists ([Cys4, Cys10]-alpha-MSH) or totally inactive (Ac[Cys4, Cys10]-alpha-MSH4-10-NH2) on fish melanocytes. These results point out some rather remarkable differences between S. marmoratus and tetrapod melanophores relative to structural requirements for MSH receptor recognition and signal transduction.


Relative cerebellar weight: a potential indicator of developmental neurotoxicity.
Overt malformations do not always accompany behavioral changes resulting from perinatal exposure to certain drugs. However, the central nervous system (CNS) is the anatomical substrate for behavior, and functional defects may be accompanied by more subtle, structural alterations of the brain. The purpose of this study was to determine if changes in the weights of certain brain regions occur in rats exposed prenatally and/or perinatally to propylthiouracil (PTU) which retards functional development of the brain. Pregnant rats were dosed with PTU during gestation and/or lactation, and on postnatal day 28, auditory startle responses were measured to determine if PTU altered functional development. The brains of all pups were then dissected into 10 separate regions, dried and individually weighed. Brain weights were expressed in absolute and relative (to total brain weight) terms. Pups that were exposed to PTU from days 10 to 21 of gestation grew normally, but their startle responses to auditory stimuli were significantly different (p less than 0.05) from controls. Thus, for the purpose of this experiment, PTU acted as a developmental neurotoxicant because it altered performance on a test of neuromuscular function without being overtly teratogenic. The weights of most brain regions in PTU-treated rats were statistically comparable to controls. However, relative cerebellar weight was significantly (p less than 0.05) different. Therefore, these data suggested that relative cerebellar weight might be used to predict functional defects that appear during development following prenatal or perinatal exposure to certain neurotoxicants. Although cerebellar weight and auditory startle responses were altered by PTU, this study does not establish a causal relationship between the anatomical and functional changes that occurred.(ABSTRACT TRUNCATED AT 250 WORDS)


The novel CGRP receptor antagonist BIBN4096BS alleviates a postoperative intestinal inflammation and prevents postoperative ileus.
Abdominal surgery results in neuronal mediator release and subsequent acute intestinal hypomotility. This phase is followed by a longer lasting inflammatory phase resulting in postoperative ileus (POI). Calcitonin gene-related peptide (CGRP) has been shown to induce motility disturbances and in addition may be a candidate mediator to elicit neurogenic inflammation. We hypothesized that CGRP contributes to intestinal inflammation and POI. The effect of CGRP in POI was tested in mice treated with the highly specific CGRP receptor antagonist BIBN4096BS and in CGRP receptor-deficient (RAMP-1(-/-) ) mice. POI severity was analyzed by cytokine expression, muscular inflammation and gastrointestinal (GI) transit. Peritoneal and muscularis macrophages and mast cells were analyzed for CGRP receptor expression and functional response to CGRP stimulation. Intestinal manipulation (IM) resulted in CGRP release from myenteric nerves, and a concurrent increased interleukin (IL)-6 and IL-1β transcription and leukocyte infiltration in the muscularis externa and increased GI transit time. CGRP potentiates IM-induced cytokine transcription within the muscularis externa and peritoneal macrophages. BIBN4096BS reduced cytokine levels and leukocyte infiltration and normalized GI transit. RAMP1(-/-) mice showed a significantly reduced leukocyte influx. CGRP receptor was expressed in muscularis and peritoneal macrophages but not mast cells. CGRP mediated macrophage activation but failed to induce mast cell degranulation and cytokine expression. CGRP is immediately released during abdominal surgery and induces a neurogenic inflammation via activation of abdominal macrophages. BIBN4096BS prevented IM-induced inflammation and restored GI motility. These findings suggest that CGRP receptor antagonism could be instrumental in the prevention of POI.


Interaction between elongation factors 1beta and 1gamma from Bombyx mori silk gland.
Elongation factor 1 (EF-1) from the silk gland of Bombyx mori consists of four subunits: alpha (51 kDa), beta (26 kDa), gamma (49 kDa), and delta (33 kDa). The EF-1alpha subunit catalyzes the binding of aminoacyl-tRNA to the ribosome concomitant with the hydrolysis of GTP. The EF-1alpha-bound GDP is then exchanged for GTP by the EF-1betagammadelta complex. To facilitate analysis of the roles of the individual EF-1beta, gamma, and delta subunits in GDP/GTP exchange on EF-1alpha, we cloned the cDNAs for these subunits and expressed them in Escherichia coli. EF-1beta, EF-1gamma, and the carboxyl-terminal half of EF-1delta were expressed, purified, and examined for protein:protein interactions by gel filtration chromatography and by a quartz-crystal microbalance method. An 80-kDa species containing EF-1beta and gamma subunits in a 1:1 molar ratio was detected by gel filtration. A higher molecular weight species containing an excess of EF-1gamma relative to EF-1beta was also detected. The amino-terminal region of EF-1beta (amino acid residues 1-129) was sufficient for binding to EF-1gamma. The carboxyl-terminal half of EF-1delta did not appear to form a complex with EF-1gamma.


The Japanese 23-valent pneumococcal polysaccharide vaccine randomized clinical trial: Further reflections on the design and results.
The recent article by Gessner et al. discussed several concerns regarding the design and results of the clinical trial by Maruyama et al. in 2010 on the vaccine efficacy (VE) of 23-valent pneumococcal polysaccharide vaccine. First, Gessner et al. questioned the integrity of the study randomization and blinding. Maruyama et al. have indicated that study participants were individually randomized and blinding was maintained throughout the study. Second, Gessner et al. questioned the internal validity of the trial results. Gessner et al. applied the reported VE against pneumococcal pneumonia and assumptions to estimate how much all-cause pneumonia could be prevented resulting in a "VE" estimate of 19.5%. This estimate does not truly qualify as a VE estimate, but as vaccine effectiveness estimate from a hypothetical cohort. The randomized, placebo-controlled trial conducted by Maruyama et al. met the methodological standards for a randomized control trial and its results are unquestionably valid.


2-Aminobenzimidazoles as potent ITK antagonists: trans-stilbene-like moieties targeting the kinase specificity pocket.
Based on the information from molecular modeling and X-ray crystal structures, the kinase specificity pocket of ITK could be occupied upon extension of the right-hand-side of the 2-benzimidazole core of the inhibitors. 2-Aminobenzimidazoles with a trans-stilbene-like extension were designed and synthesized as novel ITK antagonists. Significant improvement on binding affinity and cellular activity were obtained through the trans-stilbene-like antagonists. Several compounds showed inhibitory activity in an IL-2 functional assay.


Paclitaxel, epirubicin, and carboplatin in advanced or recurrent endometrial carcinoma: a Hellenic Co-operative Oncology Group (HeCOG) study.
Taxanes, anthracyclines, and platinum compounds represent the chemotherapeutic agents with the greatest activity in metastatic endometrial carcinoma. We administered the combination of paclitaxel, epirubicin and carboplatin to patients with metastatic or recurrent carcinoma of the endometrium to evaluate its activity and to define its toxicity. Sixty-three consecutive patients were treated on an outpatient basis with epirubicin 50 mg/m(2), followed by paclitaxel 150 mg/m(2), administered intravenously over a 3-h period. Subsequently, the patients received carboplatin at AUC of 5. The chemotherapy was repeated every 3 weeks with granulocyte colony-stimulating factor (G-CSF) support for a maximum of six courses. Response was assessed among 56 eligible patients. Thirty-six (63.2%) patients achieved objective clinical response (95% CI, 50.6-75.7%) including 14 (24.6%) complete and 22 (38.6%) partial responses. The median duration of response was 7.9 months, and the median times to progression and survival for all patients were 7.8 and 13.8 months, respectively. Grade 3 or 4 neutropenia occurred in 9 (15.5%) patients but only 3 episodes of neutropenic fever were encountered. Grade 2 or 3 neurotoxicity was observed in 19% of patients. Two patients died of sudden cardiac death 10 and 14 days after the administration of the first chemotherapy cycle, respectively, but these deaths were not clearly treatment related. The combination of paclitaxel, epirubicin and carboplatin with G-CSF support appears active in patients with metastatic or recurrent carcinoma of the endometrium.


"That's why people don't call 911": Ending routine police attendance at drug overdoses.
Research has shown that police attendance and the corresponding threat of criminal charges are major deterrents to people seeking emergency medical assistance in the event of an overdose. In response to these barriers, Canada passed the Good Samaritan Drug Overdose Act in 2017, providing immunity from prosecution for simple drug possession to overdose victims or bystanders who phone 911. In theory, this should make people more comfortable seeking emergency supports, but in practice our research found that many remain hesitant because police continue to be routinely dispatched to the overdose site. Based on focus groups and surveys with 109 people who use drugs across Ontario, Canada, our findings show that the vast majority of participants have negative interactions with police, which discourages them from seeking medical assistance at future overdose incidents. Almost all questioned the necessity of dispatching law enforcement to a health emergency that requires medical intervention. As such, this commentary draws on the study's qualitative data to argue that ending routine police attendance at drug overdoses in Ontario would remove a major barrier to calling 911, and thus prevent the further, unnecessary loss of life in the ongoing overdose crisis.


Injury of myocardial conduction tissue and coronary artery smooth muscle following brain death in the baboon.
Experimental brain death was induced in 36 chacma baboons. In group A (n = 17), brain death was induced with no pharmacologic or surgical manipulation. Group B (n = 7) underwent bilateral vagotomy, unilateral left cardiac sympathectomy, or bilateral adrenalectomy before induction of brain death. Group C (n = 7) underwent total cardiac sympathectomy. Group D (n = 5) was pretreated with verapamil hydrochloride. Following induction of brain death, group A animals were maintained on a ventilator for a mean of 12 hr and 6 hr for the remaining groups. At the end of the experiment, the heart was excised, and tissue blocks were examined with light microscopy at (A) the atriaventricular node-bundle of His; (B) the major coronary arteries; and (C) myocardial tissue from the ventricular septum or left ventricular wall. In group A, 41% of the hearts showed histologic features of injury to the conduction tissue, 70% presented contraction band necrosis of the smooth muscle of the coronary arteries, and an incidence of 100% of the groups showed myocyte injury, more evident in the subendocardial area. In group B animals, conduction tissue injury was seen in 6 animals; the coronary arteries were not examined in this group; the incidence of myocyte injury was seen in 80% of the animals. Animals in groups C and D show no histopathologic injury in the conduction tissue (group A vs. C P less than 0.04), nor in the coronary arteries (group A vs. C P less than 0.002; group A vs. D P less than 0.01), preserving the myocytes (P less than 0.001). The catecholamine storm associated to acute increment of the endocranial pressure at the time of induction of brain death induces major histopathologic changes in the myocardium, as a result of endogenous catecholamines released inducing calcium overflow injury, affecting the conduction tissue, the smooth muscle of the coronary arteries, and the contractile myocardium. This can be prevented by calcium blockers or cardiac denervation.


Long-term outcomes after lower extremity bypass in the actively smoking claudicant.
Smoking is known to increase complications, including poor wound healing, coagulation abnormalities, and cardiac and pulmonary ramifications. Across specialties, elective surgical procedures are commonly denied to active smokers. Given the base population of active smokers with vascular disease, smoking cessation is encouraged but is not required the way it is for elective general surgery procedures. We aim to study the outcomes of elective lower extremity bypass (LEB) in actively smoking claudicants. We queried the Vascular Quality Initiative Vascular Implant Surveillance and Interventional Outcomes Network LEB database from 2003 to 2019. In this database we found 609 (10.0%) never smokers (NS), 3388 (55.3%) former smokers (FS), and 2123 (34.7%) current smokers (CS) who underwent LEB for claudication. We performed two separate propensity score matches without replacement on 36 clinical variables (age, gender, race, ethnicity, obesity, insurance, hypertension, diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, previous coronary artery bypass graft, carotid endarterectomy, major amputation, inflow treatment, preoperative medications and treatment type), one of FS to NS and a second analysis of CS to FS. Primary outcomes included 5-year overall survival (OS), limb salvage (LS), freedom from reintervention (FR), and amputation-free survival (AFS). Propensity score matches resulted in 497 well-matched pairs of NS and FS. In this analysis we found no difference in terms of OS (HR, 0.93; 95% CI, 0.70-1.24; P = .61), LS (HR, 1.07; 95% CI, 0.63-1.82; P = .80), FR (HR, 0.9; 95% CI,0.71-1.21; P = .59), or AFS (HR, 0.93; 95% CI,0.71-1.22; P = .62). In the second analysis, we had 1451 well-matched pairs of CS and FS. There was no difference in LS (HR, 1.36; 95% CI,0.94-1.97; P = .11) or FR (HR, 1.02; 95% CI,0.88-1.19; P = .76). However, we did find a significant increase in OS (HR, 1.37; 95% CI,1.15-1.64, P <.001) and AFS (HR, 1.38; 95% CI,1.18-1.62; P < .001) in FS compared with CS. Claudicants represent a unique nonemergent vascular patient population that may require LEB. Our study found that FS have better OS and AFS when compared with CS. Additionally, FS mimic nonsmokers at 5-year outcomes for OS, LS, FR, and AFS. Therefore, structured smoking cessation should be a more prominent part of vascular office visits before elective LEB procedures in claudicants.


Turnover of excess hemoglobin alpha chains in beta-thalassemic cells is ATP-dependent.
Blood erythroid cells from five beta-thalassemic donors were incubated with [3H]leucine at 37 degrees C to label the pool of excess, free hemoglobin alpha chains. The 3H-labeled cells were split and reincubated in nonradioactive media that either supported ATP production (with 5 mM glucose) or inhibited ATP production (without glucose but with 20 mM 2-deoxyglucose and 0.20 mM 2,4-dinitrophenol). During the 6-h incubation in the glucose medium, the total cellular protein 3H radioactivity decreased about 30%, while the ATP levels remained constant. Chromatographic separation of the alpha- and non-alpha-globin chains of the crude (stroma included) lysates and electrophoretic separation of the free alpha chains and tetrameric hemoglobins of the stroma-free soluble phases both showed that degradation of the alpha chains was responsible for the decrease in protein 3H radioactivity. Conversely, in the energy-deprived cells, the ATP levels dropped to less than 10% of that of the energy-supported cells, and the turnover of alpha-globin 3H radioactivity of the crude lysates was only 5-10%. These results indicate that proteolysis of excess, newly synthesized alpha chains in beta-thalassemic cells is ATP-dependent. The accumulation, mostly in the stromal fraction, of intact 3H-alpha chains in the ATP-deprived cells suggests that an ATP-dependent step occurs early in the biochemical pathway of alpha chain proteolysis. Denaturation resulting in insolubility of the free alpha chains may be a recognition signal for activation of this proteolysis.


Intradiscal methylene blue injection for the treatment of chronic discogenic low back pain.
This article was a preliminary report of prospective clinical trial of a group of patients with chronic discogenic low back pain who met the criteria for lumbar interbody fusion surgery but were treated instead with an intradiscal injection of methylene blue (MB) for the pain relief. Twenty-four patients with chronic discogenic low back pain underwent diagnostic discography with intradiscal injection of MB. The principal criteria to judge the effectiveness included alleviation of pain, assessed by visual analog scale (VAS), and improvement in disability, as assessed with the Oswestry Disability Index (ODI) for functional recovery. The mean follow-up period was 18.2 months (range 12-23 months). Of the 24 patients, 21 (87%) reported a disappearance or marked alleviation of low back pain, and experienced a definite improvement in physical function. A statistically significant and clinically meaningful improvement in the changes in the ODI and the VAS scores were obtained in the patients with chronic discogenic low back pain (P=0.0001) after the treatment. The study suggests that the injection of MB into the painful disc may be a very effective alternative for the surgical treatment of chronic discogenic low back pain.


[Treatment of iron deficiency anaemia in pregnant, puerperal and gynaecological patients--different drugs, different approaches].
According to WHO about 50 per cent of women of fertile age have iron deficiency anaemia (IDA). Iron loss > 80 mg per month, with menstruation in 22 per cent of women cause a negative iron balance in the course of time. About 40 per cent of women have data of prelatent iron deficiency still before conception, and if the demands of occured pregnancy are added, IDA is quickly reached. Over 30 per cent of puerperal women are affected by anaemia. To make a pharmacoeconomic assessment of peroral antianaemic drugs used for treatment of IDA in pregnant, puerperal and gynaecologically ill women. There are presented- daily intake of drugs, number of drug package taken, the price of a drug package, value of treatment a month, reimbursement of the drugs below: Ferro Gradumet, Maltofer Fol, Sorbifer Durules, Tot'hema, Legofer, Ferro-Folgamma, Tardiferon. The survey made and the data of own studies show that the most important in treatment of IDA are the choice of iron- containing drug and the correct therapeutic approach. The choice of peroral iron- containing therapy is determined by: high "patient compliance"--good tolerance, independence on food intake, once daily intake, low frequency of adverse effects and treatment with low price (economic effect). The most suitable for treatment of IDA in pregnant and puerperal women are Maltofer Fol and Sorbifer Durules. Maltofer Fol is with the best correlation price: "patient compliance". Tot'hema and Legofer have a good tolerance, a few adverse effects, but they are with high price. Ferro folgamma has not a high "patient compliance" and it has comparatively high price. Ferro gradumet has a low price and low "patient compliance".


Specific osteogenesis imperfecta-related Gly substitutions in type I collagen induce distinct structural, mechanical, and dynamic characteristics.
The stiffnesses, β-structures, hydrogen bonds, and vibrational modes of wild-type collagen triple helices are compared with osteogenesis imperfecta-related mutants using integrative structural and dynamic analysis via molecular dynamics simulations and Markov state models. Differences in these characteristics are strongly related to the unwound structural states in the mutated regions that are specific to each mutation.


Short-term exercise increases GDNF protein levels in the spinal cord of young and old rats.
Neurotrophic factors may play a role in exercise-induced neuroprotective effects, however it is not known if exercise mediates changes in glial cell line-derived neurotrophic factor (GDNF) protein levels in the spinal cord. The aim of the current study was to determine if 2 weeks of exercise alters GDNF protein content in the lumbar spinal cord of young and old rats. GDNF protein was quantified via an enzyme-linked immunosorbent assay and Western blot. Immunohistochemical analysis localized GDNF in choline acetyltransferase (ChAT)-positive motor neurons and cell body areas were measured. Involuntary running in the young animals appeared to elicit the greatest increase in GDNF protein content (sixfold increase), followed by swimming (threefold increase) and voluntary running (twofold increase); however there was no significant difference between the modalities of exercise. Low-intensity running of the old animals significantly increased GDNF protein content in the spinal cord. Both young and old exercised animals showed a doubling in ChAT-positive motor neuron cell body areas. These results suggest that GDNF protein content in the spinal cord is modulated by exercise.


Overexpression of long intergenic noncoding RNAs in bladder cancer: A new insight to cancer diagnosis.
There is increasing evidence that show long noncoding RNAs including long intergenic noncoding RNAs (lincRNA) play a pivotal regulatory role in the biological processes. Differential expression of lincRNAs can be utilized for cancer diagnosis, prognosis, and targeted therapy. Little is known about their expressions in urothelial tumors. Concerning the potential role of lincRNAs in cancer development, we aimed to investigate the expression levels of LINC00958 and DNM3OS in bladder cancer. Fifty tumor and 50 adjacent non-tumor tissue samples along with their clinicopathological parameters were obtained from bladder cancer patients. Expressions of LINC00958 and DNM3OS were analyzed by Real-time PCR. ROC curve analysis was used to evaluate the diagnostic power of LINC0095 and DNM3OS for BC. Expression level of LINC00958 was considerably increased in cancerous tissues (P < 0.001) and in correlation with cigarette smoking (P = 0.043). DNM3OS expression was higher in the tumor tissues than normal tissues (P < 0.001) and showed a significant association with age (P = 0.038). By using the ROC curve, the diagnostic power of LINC00958 and DNM3OS transcript levels in bladder cancer were estimated to be 87% and 75%, respectively. Our findings offer some important intuitions into the oncogenic role of LINC00958 and DNM3OS in bladder cancer and suggest that they can be candidate biomarkers and may provide new approaches for the diagnosis and therapy if being validated in a larger sample size of clinical samples as well as functional studies.


The effect of CYP2J2, CYP3A4, CYP3A5 and the MDR1 polymorphisms and gender on the urinary excretion of the metabolites of the H-receptor antihistamine ebastine: a pilot study.
To determine the effect of gender and the genetic polymorphisms of CYP2J2, CYP3A4, CYP3A5 and MDR1 on the urinary excretion of the H(1) antihistamine ebastine in healthy subjects. Eighty-nine Caucasians were studied. The presence of polymorphisms in genes known to be involved in ebastine metabolism and transport (CYP2J2*2,*3,*4,*6,*7, CYP3A4*1B, CYP3A5*3, *6 and MDR1(ABCB1)(C3435T)) was assessed by means of PCR-restriction fragment length polymorphism and sequencing methods. Genotype was correlated with the urinary excretion of the main ebastine metabolites (desalkylebastine and carebastine) under basal conditions and after administration of grapefruit juice. Women excreted statistically greater amounts of desalkylebastine in urine (mean +/- SD (95% confidence intervals, 95% CI), 23.0 +/- 19.5 (18.1, 27.9) micromol) than men (12.4 +/- 11.0 (7.9, 16.9)), (mean difference: 10.6 (2.4, 18.7), P < 0.005). The CYP2J2, CYP3A4 and CYP3A5 analysed polymorphisms did not greatly affect ebastine metabolite excretion. The MDR1(C3435T) polymorphism was found to affect both the urinary excretion of the active metabolite carebastine (32.3 +/- 18.3 (23.1, 41.4), 22.8 +/- 14.7 (18.6, 27.0) and 21.5 +/- 15.3 (14.7, 28.3) for CC, CT and TT carriers, respectively; P < 0.05) and the grapefruit juice-induced inhibition of its transport/formation (mean fold-decrease +/- SD (95% CI), 1.5 +/- 0.8 (1.0, 2.0), 1.1 +/- 0.9 (0.7, 1.4) and 0.9 +/- 0.4 (0.6, 1.2) for CC, CT and TT carriers, respectively; P = 0.01). Gender and the presence of the MDR1(C3435T) polymorphism both influence the excretion of ebastine metabolites in urine.


Effects of intrathecal opioids combined with low-dose naloxone on motilin and its receptor in a rat model of postoperative pain.
To investigate the effects of intrathecal morphine and fentanyl combined with low-dose naloxone on the expression of motilin and its receptor in a rat model of postoperative pain. An intrathecal catheter was implanted, and saline, opioids (morphine and fentanyl) and naloxone were intrathecally administered 7 days later. An incisional pain model was established to induce pain behaviors in rats by unilateral plantar incision. Thermal hyperalgesia and mechanical allodynia were measured by using a radiant heat and electronic Von Frey filament, respectively. The expression of motilin in the hippocampus, stomach, duodenum, and plasma was determined by ELISA; and the expression of motilin receptor in the hippocampus was detected by Western blot assay. Motilin and its receptor were detected in the hippocampus. Acute incisional pain increased the motilin expression in the hippocampus and duodenum, while decreasing its expression in the gastric body and plasma. Postoperative analgesia with morphine+fentanyl upregulated the expression of motilin in the hippocampus; however, motilin was downregulated in peripheral sites. Naloxone at 1 ng/kg restored motilin to baseline levels. Acute pain, morphine+fentanyl, and naloxone all induced the expression of motilin receptor in the hippocampus. Acute pain, postoperative analgesia with opioids, and naloxone significantly impacted the expression of hippocampal and peripheral motilin. Variation trends in all sites were not identical. Intrathecal injection of low-dose naloxone upregulated paw withdrawal thermal latency and enhanced the analgesic effects of opioids. The findings presented here provide a new basis for central and peripheral regulations in GI motility, clinical postoperative analgesia, and management of analgesic complications.


Adhesive-enhanced sternal closure to improve postoperative functional recovery: a pilot, randomized controlled trial.
We previously established a proof-of-concept in a human cadaveric model where conventional wire cerclage was augmented with a novel biocompatible bone adhesive that increased mechanical strength and early bone stability. We report the results of a single-center, pilot, randomized clinical trial of the effects of adhesive-enhanced closure of the sternum on functional postoperative recovery. In 55 patients undergoing primary sternotomy, 26 patients underwent conventional wire closure and were compared with 29 patients who underwent adhesive-enhanced closure, which consisted of Kryptonite biocompatible adhesive (Doctors Research Group Inc, Southbury, CT) applied to each sternal edge in addition to conventional 7-wire cerclage. Patients were monitored postoperatively at 72 hours, weekly for 12 weeks, and then after 12 months for incisional pain, analgesic use, and maximal inspiratory capacity measured by spirometry. Standardized assessment tools measured postoperative physical disability and health-related quality of life. No adverse events or sternal complications from the adhesive were observed early or after 12 months. Incisional pain and narcotic analgesic use were reduced in adhesive-enhanced closure patients. Inspiratory capacity was significantly improved, postoperative health-related quality of life scores normalized more rapidly, and physical disability scores were reduced. Computed tomography imaging was suggestive of sternal healing. Adhesive-enhanced closure is a safe and simple addition to conventional wire closure, with demonstrated benefits on functional recovery, respiratory capacity, incisional pain, and analgesic requirements. A large, multicenter, randomized controlled trial to examine the potential of the adhesive to prevent major sternal complications in higher risk patients is warranted.


WISP2 exhibits its potential antitumor activity via targeting ERK and E-cadherin pathways in esophageal cancer cells.
Emerging evidence has demonstrated that WISP2 is critically involved in cell proliferation, migration, invasion and metastasis in cancers. However, the function of WISP2 in esophageal squamous cell carcinoma (ESCC) is largely unclear. Therefore, we aim to explore the effects and the potential mechanism of WISP2 on proliferation and motility and invasion of ESCC cells. Cell proliferation was detected by MTT assay and apoptosis was measured by FACS in ESCC cells after WISP2 downregulation and overexpression. Cell migration and invasion were analyzed by wound healing assay and transwell migration assay, respectively. The expression of ERK-1/2, Slug and E-cadherin was measured by Western blot respectively. IHC was performed to measure the expression of WISP2 in ESCC tissues. WISP2 overexpression is associated with survival in ESCC patients. WISP2 overexpression inhibited cell growth and induced cell apoptosis, suppressed cell migration and invasion in ESCC cells. Moreover, WISP overexpression retarded tumor growth in mouse model. WISP2 downregulation enhanced cell growth, inhibited apoptosis, promoted cell migration and invasion in ESCC cells. Mechanistically, WISP2 exerts its tumor suppressive functions via regulation of ERK1/2, Slug, and E-cadherin in ESCC cells. Our findings suggest that activation of WISP2 could be a useful therapeutic strategy for the treatment of ESCC.


Effect of phenol formaldehyde-associated microplastics on soil microbial community, assembly, and functioning.
Increasing investigations explore the effects of plastic pollutants on bacterial communities, diversity, and functioning in various ecosystems. However, the impact of microplastics (MPs) on the eukaryotic community, microbial assemblages, and interactions is still limited. Here, we investigated bacterial and micro-eukaryotic communities and functioning in soils with different concentrations of phenol formaldehyde-associated MPs (PF-MPs), and revealed the factors, such as soil properties, microbial community assembly, and interactions between microbes, influencing them. Our results showed that a high concentration (1%) of PF-MPs decreased the microbial interactions and the contribution of deterministic processes to the community assembly of microbes, and consequently changed the communities of bacteria, but not eukaryotes. A significant and negative relationship was determined between N2O emission rate and functional genes related to nitrification, indicating that the competitive interactions between functional microbes would affect the nitrogen cycling of soil ecosystem. We further found that vegetable biomass weakly decreased in treatments with a higher concentration of PF-MPs and positively related to the diversity of micro-eukaryotic communities and functional diversity of bacterial communities. These results suggest that a high concentration of the PF-MPs would influence crop growth by changing microbial communities, interactions, and eukaryotic and functional diversity. Our findings provide important evidence for agriculture management of phenol formaldehyde and suggest that we must consider their threats to microbial community compositions, diversity, and assemblage in soils due to the accumulation of PF-MPs widely used in the field.


Deciphering the characterization, ecological function and assembly processes of bacterial communities in ship ballast water and sediments.
Various microorganisms are transported worldwide via the water and sediments inside ship ballast tanks. Nevertheless, the ecological functions and assembly processes of bacterial communities in ballast water and sediments remain poorly understood. Here, we investigated the bacterial composition, community assembly processes, and putative functions through analyses of 70 ballast water and sediment samples obtained from various ships. The results showed that the ballast sediments contained a higher diversity of bacterial communities, whereas the ballast water was characterized by the dominance of Proteobacteria. Both the composition and potential function structures of bacterial communities were clearly different between the ballast water and sediment samples. The ballast water exhibited an abundance of microorganisms that involved in sulfur oxidation, whereas the bacterial species associated with nitrogen metabolism were abundant in the sediments. Co-occurrence network analysis revealed that the communities in ballast sediment samples possessed more complex network structures with higher modularity and positive associations among bacterial populations. Stochastic processes, especially the dispersal limitation process played the most important influence in the assembly of the communities in ballast water. Meanwhile, the bacterial communities in the ballast sediments were primarily governed by the homogeneous selection of determinacy. The results from this study will help us understand the ecological processes related to the bacterial communities in the ballast tanks and provide a foundation for the management of ballast water and sediments.


Identification of the sites of selective phosphorylation and dephosphorylation of the rat brain Na+ channel alpha subunit by cAMP-dependent protein kinase and phosphoprotein phosphatases.
Voltage-sensitive brain Na+ channels are regulated by cAMP-dependent protein kinase (cA-PK) and protein kinase C. Using synthetic peptides and protein microsequencing, we have determined that the alpha subunit of rat brain Na+ channel is selectively phosphorylated by cA-PK in vitro and in intact cells on 4 serine residues in the intracellular loop connecting homologous domains I and II. Ser-623 was most rapidly and extensively phosphorylated in vitro, whereas Ser-573, Ser-610, and Ser-687 were phosphorylated to lesser extents. In contrast, serine 687 was most extensively phosphorylated in mammalian cells transfected with the alpha subunit of type IIA Na+ channel in response to an increase in intracellular cAMP. Purified protein phosphatases dephosphorylated these sites selectively. Calcineurin rapidly and extensively dephosphorylated Ser-623 and also dephosphorylated Ser-573, Ser-610, and Ser-687 to lesser extents. Phosphatase 2A selectively dephosphorylated Ser-610. Together these results indicate that modulation of neuronal Na+ channel activity and therefore neuronal excitability by cAMP-dependent phosphorylation results from selective phosphorylation and dephosphorylation of four sites in the intracellular loop connecting homologous domains I and II of the alpha subunit.


A small group of committed people.
This article recounts the author's personal experience with a flawed medication reconciliation system that was improved through her initiative and persistence. The history, function, and value of the nurse navigator role in identifying barriers to care are described. The author advocates for expanding our horizons beyond navigation to address and eliminate the identified barriers to provide high-quality patient and family care.


Self-Assembly of Perovskite CsPbBr3 Quantum Dots Driven by a Photo-Induced Alkynyl Homocoupling Reaction.
Herein, we report the facile growth of three-dimensional CsPbBr3 perovskite supercrystals (PSCs) self-assembled from individual CsPbBr3 perovskite quantum dots (PQDs). By varying the carbon chain length of a surface-bound ligand molecule, 1-alkynyl acid, different morphologies of PSCs were obtained accompanied by an over 1000-fold photoluminescence improvement compared with that of PQDs. Systematic analyses have shown, for the first time, that under UV irradiation, CsBr, the byproduct formed during PQDs synthesis, could effectively catalyze the homocoupling reaction between two alkynyl groups, which further worked as a driving force to push forward the self-assembly of PQDs.


Brugada-like electrocardiographic pattern induced by an episode of anemia.
The mechanisms responsible for the undulating pattern of ST-segment elevations in the Brugada syndrome are still a matter of discussion. This report describes a young man with a Brugada-like electrocardiographic pattern. The specific ST-segment elevations were unmasked during an episode of anemia due to a duodenal ulcer.


Impact of waste dump on surface water quality and aquatic insect diversity of Deepor Beel (Ramsar site), Assam, North-east India.
Water and aquatic insects were collected seasonally from site 1, the low-lying area of the dump near Deepor Beel, and from sites 2 and 3 of the main wetland and analysed. While dissolved oxygen (DO) increased from site 1 to site 3 in each season, electrical conductivity (EC), total dissolved solid (TDS), total alkalinity (TA) and free CO2 (F-CO2) decreased. Pb and Cd were found to exceed the limits set for drinking water in all the sites and seasons. Species richness (SpR) was found highest (23) at site 2 and lowest (14) at site 1. Sensitive species was absent. The Shannon (H') values at site 1 were < 1 while at sites 2 and 3 were > 1 in most of the seasons. Biological monitoring scores (Biological Monitoring Working Party and Stream Invertebrate Grade Number-Average Level) in different sites and seasons inferred severely poor to moderate water quality. At site 1, significant negative correlations were seen for Pb and Cr with SpR while Ni and Cu with insect density (ID). At site 2, TA had highly significant positive correlations with SpR and ID while Cu showed negative correlation with SpR. At site 3, ID had significant negative relationships with air temperature, water temperature, depth, TA, F-CO2, PO43- and Cr. Canonical correspondence analysis triplot has clearly separated site 1 associated with tolerant species and highly influenced by TA, TDS, EC, F-CO2, Cr, Ni, Cd and Zn confirming high anthropogenic activities on that site. Tolerant and semitolerant species were present at site 2 (influenced by depth and transparency) and site 3 (influenced by Pb and WT) both. Results of this study discerned that the dump site is the point source of pollution.


Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers.
Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS. We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes. In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1β, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-β1, IgE, Staphylococcus aureus enterotoxin-specific IgE, and albumin. We used partition-based clustering. Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5-negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a TH17 profile and had mixed CRSsNP/CRSwNP. The IL-5-positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin-specific IgE. Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only.


CRISPR/Cas9 genome engineering in hematopoietic cells.
The development of genome editing tools capable of modifying specific genomic sequences with unprecedented accuracy has opened up a wide range of new possibilities in targeted gene manipulation. In particular, the CRISPR/Cas9 system, a repurposed prokaryotic adaptive immune system, has been widely adopted because of its unmatched simplicity and flexibility. In this review we discuss achievements and current limitations of CRISPR/Cas9 genome editing in hematopoietic cells with special emphasis on its potential use in ex vivo gene therapy of monogenic blood disorders, HIV and cancer.


Fresh frozen cadaver workshops for advanced vascular surgical training.
Reduction in working hours, streamlined training schemes and increasing use of endovascular techniques has meant a reduction in operative experience for newer vascular surgical trainees, especially those exposures which are not routinely performed such as thoracoabdominal, thoracotomy and retroperitoneal aortic, for example. This paper describes an Advanced Anatomy of Exposure course which was designed and convened at the Clinical Training & Evaluation Centre in Western Australia and uses fresh frozen cadavers. Feedback was obtained from the participants who attended over three courses by questionnaire. Feedback was strongly positive for the course meeting both its learning outcomes and personal learning objectives, and in addition, making a significant contribution to specialty skills. Most participants thought the fresh frozen cadaveric model significantly improved the learning objectives for training. The fresh frozen cadaver is an excellent teaching model highly representative of the living open surgical scenario where advanced trainees and newly qualified consultants can improve their operative confidence and consequently patient safety in vascular surgery. An efficient fresh frozen cadaver teaching programme can benefit many health professionals simultaneously maximizing the use of donated human tissue.


Idiopathic bilateral carpal tunnel syndrome in a 9-month-old infant presenting as a pseudo-dystonia.
Carpal tunnel syndrome is the most common focal peripheral neuropathy seen in most electrophysiological laboratories. Although the incidence of carpal tunnel syndrome in adults is 50 to 150 cases per 100,000 people, it is rare in children. There are less than 200 case reports of carpal tunnel syndrome in children, with mucopolysaccharides and mucolipidosis being the most frequent cause. Idiopathic carpal tunnel syndrome with childhood onset occurs in less than 0.2% of cases. We describe a 9-month-old infant who presented with intermittent abnormal posturing movement of both hands. The clinical presentation and the electrophysiological studies confirmed the diagnosis of carpal tunnel syndrome. His dystonic posturing had disappeared completely 3 weeks after surgical release of both flexor retinaculi. We are not only reporting the youngest child with carpal tunnel syndrome, but we also report a new cause of abnormal movement disorder in children.


Wheel-running reinforcement in free-feeding and food-deprived rats.
Rats experiencing sessions of 30min free access to wheel running were assigned to ad-lib and food-deprived groups, and given additional sessions of free wheel activity. Subsequently, both ad-lib and deprived rats lever pressed for 60s of wheel running on fixed ratio (FR) 1, variable ratio (VR) 3, VR 5, and VR 10 schedules, and on a response-initiated variable interval (VI) 30s schedule. Finally, the ad-lib rats were switched to food deprivation and the food-deprived rats were switched to free food, as rats continued responding on the response-initiated VI 30-s schedule. Wheel running functioned as reinforcement for both ad-lib and food-deprived rats. Food-deprived rats, however, ran faster and had higher overall lever-pressing rates than free-feeding rats. On the VR schedules, wheel-running rates positively correlated with local and overall lever pressing rates for deprived, but not ad-lib rats. On the response-initiated VI 30s schedule, wheel-running rates and lever-pressing rates changed for ad-lib rats switched to food deprivation, but not for food-deprived rats switched to free-feeding. The overall pattern of results suggested different sources of control for wheel running: intrinsic motivation, contingencies of automatic reinforcement, and food-restricted wheel running. An implication is that generalizations about operant responding for wheel running in food-deprived rats may not extend to wheel running and operant responding of free-feeding animals.


Diverticular disease: electrophysiologic study and a new concept of pathogenesis.
The cause of diverticular disease (DD) is not exactly known, although colonic motor disorder has been proposed as a factor in the pathogenesis of the condition. We investigated the hypothesis that disordered colonic electrical activity is responsible for the colonic motor dysfunction and the development of DD. The electromyographic (EMG) activity and pressure of the sigmoid colon (SC) were recorded in 36 patients [16 early cases, 20 advanced cases; age (mean +/- SD) 53.3 +/- 5.6 years; 19 women, 17 men] and 22 healthy volunteers. The percutaneous route was used for recording the SC EMG. The healthy volunteers exhibited SC slow waves with a regular rhythm and the same frequency, amplitude, and conduction velocity from the three electrodes in the same subject. The SC basal pressure (7.9 cm H(2)O) was interrupted by bouts of high pressure (26.8 cm H(2)O). The early-DD cases showed slow waves with an irregular rhythm and significantly higher variables ( p < 0.05) than the volunteers. Action potentials followed randomly or were superimposed on the slow waves. The SC basal pressure was significantly higher than that of the volunteers (21.4 cm H(2)O, p < 0.01). Bouts of pressure (58.6 cm H(2)O) coupled with action potentials were recorded. No waves were recorded from 15 of 20 of the advanced-DD patients. In 5 patients, slow waves with an irregular rhythm and lower variables ( p < 0.05) than those of the volunteers were recorded. The basal SC pressure was significantly above normal. Three electrical activity patterns could be identified in DD patients: "tachyrhythmic" in the early-DD patients and "bradyrhythmic" or "silent" in the late-DD patients. These dysrhythmias may result from a disordered colonic pacemaker. The similarity between early DD and the irritable bowel syndrome suggests that DD is an advanced stage of the irritable bowel syndrome; studies are required to investigate this hypothesis further.


Changes in motoneurone firing rates during sustained maximal voluntary contractions.
Tungsten micro-electrodes have been used to record the electrical activity of single motor units in the human adductor pollicis during maximal voluntary contractions. The potentials were characteristic of those from single muscle fibres. In brief maximal contractions, the firing rates of over 200 motor units were obtained from five normal subjects. Four subjects had a similar range (mean 26.4 +/- 6.5 Hz) while the fifth was slightly higher (35 +/- 7.4 Hz). When maximal voluntary force was sustained for 40-120 s, there was a progressive decline in the range and mean rate of motor-unit discharge. In the first 60 s, mean rates fell from about 27 Hz to 15 Hz. There was some evidence to suggest that those units with the highest initial frequencies changed rate most rapidly. It is suggested that this decline in motor unit discharge rates is not responsible for force loss, but that it may enable effective modulation of voluntary strength by rate coding to continue during fatigue.


Rational approach to the wheezy infant.
The infant or child presenting to the physician's office with persistent or recurrent wheezing during the first two year's of life poses a diagnostic dilemma. A careful medical history should document risk factors for persistent wheezing, including maternal smoking, feeding practices, environmental history, and family history of asthma or cystic fibrosis (CF). A suggested diagnostic approach to the causes of infantile wheezing is outlined. A chest radiograph is non-specific, but may suggest a congenital airway anomaly. Infant pulmonary function testing (IPFT) can help differentiate between central airflow (intrathoracic, extrathoracic, or fixed) and peripheral airflow obstruction. The infant with either intrathoracic, extrathoracic, or fixed airflow obstruction on the PFT may benefit from flexible fiberoptic bronchoscopy. The infant with either an intrathoracic or fixed airway obstruction should undergo an upper gastrointestinal (UGI) series to evaluate the anatomy for extrinsic tracheal compression. The response to treatment with anti-inflammatory therapy may suggest an inflammatory disease such as asthma or CF. The infant with peripheral airflow obstruction and a good response to bronchodilators (> or =25%) using the forced exhalation technique is given the diagnosis of infantile asthma. The infant with peripheral airflow obstruction and no response to bronchodilators should be evaluated further for possible gastroesophageal reflux disease (GERD), and for other causes, which are associated with wheezing symptoms.


Morphology, ontogeny and molecular phylogeny of a new urostylid ciliate, Bakuella (Pseudobakuella) guangdongica n. sp. (Ciliophora, Hypotrichia) from southern China.
The morphology, morphogenesis, and molecular phylogeny of Bakuella (Pseudobakuella) guangdongica n. sp., isolated from southern China, were investigated. The new species is characterized by a body length of 150-225 μm in vivo; 35-42 adoral membranelles; 3-5 buccal, two frontoterminal, 7-12 transverse and two pretransverse ventral cirri; midventral complex comprised of 10-20 pairs and two rows extending to transverse cirri; posterior part of marginal rows slightly overlapping; colorless cortical granules about 1 μm across, arranged in small groups; soil habitat. Its main ontogenetic features are: (1) in the proter, the parental adoral zone of membranelles is completely renewed by new structures; (2) in the opisthe, the oral primordium originates apokinetally, some old midventral cirri join the formation of frontoventral-transverse cirral anlagen; (3) the anlagen for marginal rows and dorsal kineties develop intrakinetally; and (4) the numerous macronuclear nodules fuse into a single mass before dividing. Phylogenetic analyses based on the SSU rDNA sequence suggest the non-monophyly of the genus Bakuella.


Exploring the perceived effectiveness and cultural acceptability of COVID-19 relevant social media intervention content among Alaska Native people who Smoke: The CAN Quit study.
Social media platforms have potential for reach and effectiveness to motivate smoking cessation and use of evidence-based cessation treatment, even during the worldwide COVID-19 pandemic. This study builds on our prior community participatory approach to developing content postings for the CAN Quit Facebook intervention among Alaska Native (AN) people who smoke. With input from a community advisory committee, we selected new content on COVID-19 preventive practices (e.g., masking) and evaluated them using a validated, six-item perceived effectiveness scale and a single item assessing cultural relevance. We obtained feedback on six content postings (two videos and four text/pictures) from an online survey administered to 41 AN people (14 men, 27 women; age range 22-61 years) who smoke in Alaska statewide with 49 % residing in rural Alaska. Perceived effectiveness scale scores were high across postings, ranging from 3.9 to 4.4 out of a maximum score of 5.0. Cultural relevance item scores ranged from 3.9 to 4.3. We found no appreciable differences by sex, age, or rural/urban location for either score. This study adds new information on the adaptation, acceptability, and perceived effectiveness of content on COVID-19 preventive practices for future inclusion in a social media-based intervention for smoking cessation specifically tailored for AN people.


Viral infections during pregnancy: a guide for the emergency physician.
Emergency physicians are frequently called on to treat or advise pregnant patients. When faced with a pregnant patient who has clinical evidence of or exposure to a viral illness, the emergency physician must be aware of the potential maternal and fetal risks posed by various viral agents. This review provides current, accurate information and guidance for the pregnant patient.


Effect of a low ethanol concentration during in vitro maturation of bovine oocytes and subsequent embryo development.
The present study investigated the effects of low ethanol exposure on bovine oocytes. Cumulus-oocyte complexes (COCs) were aspirated for the antral follicles of slaughterhouse-derived ovaries. These COCs were incubated in maturation medium containing 0, 0.1, and 0.2% ethanol for 21 h and subjected to fertilization and in vitro development, and then the rates of nuclear maturation, mitochondrial DNA copy number (Mt-cn) and protein (TOMM40), ATP content and lipid content in oocyte, fertilization, and blastulation were examined. Furthermore, COCs were incubated with 0 or 0.1% ethanol and then mitochondrial membrane potential (MMP) and the glucose consumption of COCs was determined. In addition, gene expression in oocytes was examined by RNA sequencing. Ethanol (0.1 and 0.2%) increased Mt-cn and Mt-protein levels whereas 0.2% ethanol increased the blastulation rate and ATP content in oocytes and decreased lipid content in oocytes. Ethanol (0.1%) increased MMP in oocytes and decreased glucose consumption of COCs. Eight stage embryos derived from 0.1% ethanol treated oocytes had higher levels of trimethyl-H3K9 compared with that of nontreated counterpart. RNA sequencing revealed that differentially expressed genes were associated with glycolysis/gluconeogenesis, carbon metabolism, sphingolipid metabolism, amino acid metabolism, and fatty acid degradation pathways. In conclusion, even 0.1% concentrations of ethanol during in vitro maturation considerably affects oocyte metabolism and histone configuration of embryos.


Active core structure of terfestatin A, a new specific inhibitor of auxin signaling.
The auxins, plant hormones, regulate many aspects of the growth and development of plants. Terfestatin A (TrfA), a novel auxin signaling inhibitor, was identified in a screen of Streptomyces sp. F40 extracts for inhibition of the expression of an auxin-inducible gene. However, the mode of action of TrfA has not been elucidated. To identify the active core structure, 25 derivatives of TrfA were synthesized and their inhibitory activities against auxin-inducible gene expression were evaluated. The structure-activity relationships revealed the essential active core structure of TrfA, 3-butoxy-4-methylbiphenyl-2,6-diol, which will lead to the design of biotin-tagged active TrfA.


Safety and efficacy of prophylactic gastric open peroral endoscopic myotomy for prevention of post-ESD stenosis: A case series (with video).
Endoscopic resection of over 3/4 of the lumen of the antrum or pylorus is a known risk factor for post-endoscopic submucosal dissection (ESD) stenosis. Local or systemic steroids may reduce the risk of stenosis, but their overall role in stenosis prevention remains controversial. We aimed to evaluate the efficacy and safety of prophylactic gastric open peroral endoscopic myotomy (GO-POEM) in preventing post-ESD stenosis. Ten patients who underwent GO-POEM during or immediately after ESD in the Presbyterian Medical Center between June 2017 and November 2020 were included. All patients underwent excision of over 3/4 of the lumen of the antrum or pylorus. GO-POEM was performed without submucosal tunneling. Well-differentiated tubular adenocarcinoma, tubulovillous adenoma with high-grade dysplasia, and tubular adenoma with low-grade dysplasia were diagnosed in three, one, and six patients, respectively. GO-POEM was performed successfully in all the 10 patients. Stenosis could not be evaluated in one patient, whereas one of the remaining nine patients developed post-ESD stenosis. GO-POEM decreased the risk of post-ESD stenosis in the other eight patients. Two patients presented with intraprocedural bleeding, both of whom were managed endoscopically successfully. Prophylactic GO-POEM may be a novel, effective and safe treatment modality for preventing post-ESD stenosis in the stomach. Well-designed, multicenter studies with large sample sizes are needed to confirm our results.


The earlier the better: an evaluation of changes to teaching Year 1 nuclear medicine.
In 1996 changes were made to the nuclear medicine content and mode of delivery in the Year 1 degree program at The University of Sydney, Australia. The aim was to evaluate whether changes made to the program raised the clinical abilities of students entering their clinical placement in Year 2. Questionnaires to assess the students' perception of how well Year 1 had prepared them for their clinical Year 2 were distributed to both the 1995 and 1996 students. The clinical supervisors also were surveyed to determine if the 1996 students demonstrated any difference in their understanding and application of nuclear medicine technology principles. The 1996 students were more positive about their clinical readiness and the clinical supervisors observed an increased level of understanding and application by the 1996 students. Changes in the Year 1 curriculum provided students with a higher level of clinical readiness at the commencement of their Year 2 clinical placement.


The combination of the aliphatic diamine AA0029 in ADAD vaccination system with a recombinant fatty acid binding protein could be a good alternative for the animal schistosomiasis control.
Fatty acid binding proteins (FABP) from Fasciola hepatica have demonstrated immune cross-protection against schistosomes. The present study was conducted to develop a new formulation of the recombinant FABP rFh15 with the synthetic immunomodulator AA0029 in the adjuvant adaptation (ADAD) vaccination system and to evaluate its ability to induce immune response and protection against the challenge with Schistosoma bovis cercariae. Immunization of BALB/c mice showed high levels of TNFα, IFNγ, interleukin (IL)-2, IL-6, and IL-4 in splenocyte supernatant culture and also high levels of serum specific anti-rFh15 IgG, IgG1, IgG2a IgE and IgM antibodies suggesting a mixed Th1/Th2 immune response. Using this approach, high levels of protection against experimental challenge with S. bovis cercariae were observed in the mouse and hamster models. A marked reduction up to 64% in worm burden, as well as in the number of eggs retained in liver (66%) and intestine (77%) and hepatic lesions (42%), was achieved in vaccinated BALB/c mice. Golden hamsters vaccinated and challenged in similar conditions had reductions in recovered worms (83%), liver eggs (90%), intestine eggs (96%), liver lesions (56%) and worm fecundity (48-80%). These data suggest that formulation of rFh15 in the ADAD vaccination system using the AA0029 immunomodulator could be a good option to drive an effective immunological response against schistosomiasis.


[Evaluation of the effect of bimatoprost/timolol fixed combination on ocular blood flow in patients with ocular hypertension using colour Doppler imaging. Preliminary study].
To investigate the effects of topical bimatoprost (0.3 mg/ml)/timolol maleate (5 mg/ ml) fixed combination on retrobulbar blood flow in patients with ocular hypertension (OHT). Twenty consecutive patients with OHT were prospectively randomised to either bimatoprost/timolol or placebo during a 12 weeks double masked treatment trial. Examinations were performed at baseline and after 12 weeks of treatment. Visual acuity, intraocular pressure (IOP), slit-lamp examination, automated static perimetry, systemic blood pressure and heart rate were all recorded. Retrobulbar blood flow measurements of the ophthalmic artery (AO) and central retinal artery (CRA) were measured by colour Doppler imaging. IOP was significantly decreased by bimatoprost/timolol fixed combination (p < 0.0001). Bimatoprost/timolol fixed combination therapy resulted in a significant increase in end diastolic velocity (EDV) of the CRA (p = 0.03). In patients treated with bimatoprost/timolol a statistically significant correlation between IOP and EDV was observed after 12 weeks of treatment (r = -0.511, p = 0.045). The systolic (p = 0.54) and diastolic (p = 0.67) blood pressures and heart rate (p = 0.10) did not show statistically significant differences during the study period. Topical bimatoprost/timolol fixed combination significantly reduced IOP in patients with OHT. However, the only significant change observed in retrobulbar haemodynamics was an increase in EDV of the CRA, probably associated with a reduction in IOP.


Deep hypothermia and low flow for surgery for abdominal or extraperitoneal tumors with cavoatrial extension.
Surgical treatment of retroperitoneal tumors with cavoatrial involvement can be challenging. Completeness of resection of the cava tumor extension is crucial for the patient's survival. We report a monocentric experience with the use of cardiopulmonary bypass and deep hypothermic low flow for the surgical resection of caval and atrial involvement of retroperitoneal tumors. Between 2006 and 2011, 9 patients were admitted in our cardiovascular surgery department for retroperitoneal tumors with cavoatrial extension. Every case was performed with cardiopulmonary bypass under deep hypothermia (18°C) with a continuous low-flow perfusion (1 to 1.5 L/min). Cardiopulmonary bypass output was tuned to obtain a nearly bloodless field. Reconstruction of the atriohepatic confluent was carried out with a pericardium patch without inferior vena cava reconstruction. There was no perioperative death. Mean duration of deep hypothermic low flow was 52.2 ± 18.2 minutes. The lowest mean esophageal temperature obtained during procedure was 18.2° ± 1.4°C. No neurologic event was noted postoperatively. Three patients had early complications: one reintervention for bleeding, one reintervention for mediastinitis, and one transient moderate renal failure. After a year, all patients were alive with patent atriohepatic reconstruction. Cardiopulmonary bypass with deep hypothermic low flow facilitates tumor resection and reconstruction of the atriohepatic confluent. It provides satisfactory postoperative results. It should be considered as an option in the management of these retroperitoneal tumors with cavoatrial involvement.


A hybrid of ultrathin metal-organic framework sheet and ultrasmall copper nanoparticles for detection of hydrogen peroxide with enhanced activity.
Here, we design and synthesize a novel 2D Cu-tetrakis(4-carboxyphenyl)porphyrin (TCPP) metal-organic framework (MOF) sheet and ultrasmall Cu5.4O nanoparticle (Cu5.4O USNP) hybrid (Cu-TCPP MOF/Cu5.4O nanocomposite). The graphene-like ultrathin Cu-TCPP MOF sheets offer high surface-to-volume atom ratios and many active sites, which is beneficial for loading more Cu5.4O USNPs. The Cu5.4O USNPs with ultrasmall size (<5 nm) have promising conductivity and excellent enzymatic ability for H2O2. The successfully prepared nanocomposites are characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) techniques. The 2D graphene-like ultrathin Cu-TCPP MOF sheets show no H2O2-sensing signals, whereas Cu5.4O USNPs exhibit a clear reduction peak for detection of H2O2. Interestingly, the combination of two kinds of nanomaterials improved the H2O2 sensing ability due to their synergistic effect. The properties of the unmodified electrodes and the Cu-TCPP MOF/Cu5.4O nanocomposite-modified electrodes were systemically studied by cyclic voltammetry (CV), current-time (i-t) response, and square-wave voltammetry (SWV) techniques. The electrochemical sensor for the detection of H2O2 based on the Cu-TCPP MOF/Cu5.4O nanocomposite has a lower detection limit of 0.13 μmol·L-1 and wider linear range of 0.1 × 10-6 ~ 0.59 × 10-3 mol·L-1 and 1.59 × 10-3 ~ 20.59 × 10-3 mol·L-1 when compared with the Cu5.4O USNPs-modified electrode. The electrochemical sensor can be further used to detect H2O2 produced by cells. Graphical abstract The mechanism for sensing H2O2 produced from cells based on a Cu-TCPP MOF/Cu5.4O USNPs nanocomposite-modified electrode.


Whole-body analysis of T cell responses.
In vivo methods to detect antigen-specific T cell responses at the single-cell level have greatly increased our knowledge of how the immune system works. However, most of these approaches have been confined to analysis of lymphoid tissues. Recently, the development of imaging techniques capable of simultaneously monitoring all the tissues of the body has led to the realization that antigen-experienced T cells reside in non-lymphoid tissues and may play a vital role in protecting the host against pathogens. Therefore, single-cell imaging at the level of the whole organism is needed to fully understand the dynamics of protective immunity.