Biochar-amended coastal wetland soil enhances growth of Suaeda salsa and alters rhizosphere soil nutrients and microbial communities.
Biochar has the potential to improve soil properties and increase plant productivity. However, due to the different types of soil, plants, and environmental factors, the impact of biochar is likely to vary. We explored the impacts of biochar prepared from an invasive plant Spartina alterniflora on plant performance and soil characteristics in a simulated coastal wetland ecosystem. We investigated the impact of three application ratios (control, 1%, and 5%; weight ratio) of biochar on the germination and growth of a native plant Suaeda salsa, the nutrient content and microbial community characteristics of the rhizosphere soil under three flooding treatments (no flooding, episodic flooding, and continuous flooding). Biochar application had no impact on seed germination of S. salsa, but promoted its seedling growth (biomass, height, root length) and nitrogen content. Biochar application also enhanced soil nutrient content and affected soil microbial community characteristics. Seed germination and seedling growth of S. salsa were sensitive to flooding and were the best under episodic flooding. Notably, flooding inhibited the impact of biochar on S. salsa and rhizosphere soil. In conclusion, biochar can positively affect the growth of S. salsa and improve the quality of rhizosphere soil, especially under no flooding. Our findings highlight the possibility of applying biochar for the restoration of S. salsa in coastal wetlands.


Infantile hepatic hemangiomas associated with high-output cardiac failure and pulmonary hypertension.
Infantile hepatic hemangioma (IHH) is a rare endothelial cell neoplasm, which may be concurrent with severe complications and result in poor outcomes. Moreover, the coexistence of IHH and congenial heart disease is even rarer. We present a 10-day-old male born with IHH associated with patent ductus arteriosus (PDA), atrial septal defect (ASD) and pulmonary hypertension. Moreover, we reviewed a series of studies of IHH-associated high-output cardiac failure between 1974 and 2018, and summarized the treatment outcomes. Infantile hepatic hemangioma (IHH) has been known to induce high-output heart failure. There is no literature to summarize the severity of its impact on heart, which can lead to a high mortality rate. When IHH is detected by ultrasound, the heart should be evaluated to facilitate treatment. The outcomes of IHH associated with heart failure are good.


Genetics and Epigenetics of Sex Bias: Insights from Human Cancer and Autoimmunity.
High-throughput sequencing and genome-wide association studies have revealed a sex bias in human diseases. The underlying molecular mechanisms remain, however, unknown. Here, we cover recent advances in cancer and autoimmunity focusing on intrinsic genetic and epigenetic differences underlying sex biases in human disease. These studies reveal a central role of genome regulatory mechanisms including genome repair, chromosome folding, and epigenetic regulation in dictating the sex bias. These highlight the importance of considering sex as a variable in both basic science and clinical investigations. Understanding the molecular mechanisms underlying sex bias in human diseases will be instrumental in making a first step forwards into the era of personalized medicine.


Maternal hemoglobin level and red cell indices as predictors of gestational diabetes in a multi-ethnic Asian population.
To evaluate maternal hemoglobin levels and red cell indices as predictive factors for gestational diabetes (GDM). Data from 1,538 women were analyzed. At the first visit for prenatal care, the 50-gram glucose challenge test was followed by the 75-gram glucose tolerance test in those who screened positive. GDM was diagnosed based on the WHO (1999) criteria. Maternal complete blood count was obtained at the first visit, hospitalization for birth, and after birth. Receiver operator characteristic curves were generated to establish thresholds. Multivariable logistic regression analyses were performed to establish independent predictors of GDM. GDM was diagnosed in 182/1,538 (11.8%). GDM was associated with hemoglobin level, hematocrit and erythrocyte count at the first visit for prenatal care only. Hemoglobin threshold at the first visit was established at 11.5 g/dl. After adjustment, high hemoglobin [AOR 1.5 (95% CI 1.0-2.1); p = 0.027] remained predictive of GDM. High maternal hemoglobin level at the first prenatal visit is independently predictive of GDM.


Music to reduce stress in hospitalized patients.
To determine the impact of music on the physiologic and psychological stress experienced by hospital inpatients. This pilot study monitored vital signs; utilized pain, anxiety, and agitation rating scales; and gathered verbal feedback from 50 participating inpatients at the authors' healthcare facility as they listened to music via an audiovisual interactive patient engagement technology system. After listening to music for 30 minutes, patients reported significantly lower pain and anxiety. Music offered a helpful tool to reduce pain and anxiety for patients in the ICU and telemetry units at the authors' healthcare facility. Future research may be geared toward incremental expansion and monitoring of this music intervention in other units.


The effectiveness of an intervention to reduce exposure to trace metals during or prior to pregnancy: A prospective study in urban and rural locations.
Prenatal exposure to trace metals can have adverse effects on health and increase the risk of developing certain diseases. This study aimed to determine the effectiveness of giving women advice to reduce their exposure to trace metals during pregnancy or prior to conception. The study also examined differences in exposure between rural and urban environments in southern France. In this prospective study, pregnant women or those intending to conceive were recruited from two medical centers for gynecology/obstetrics (rural location: Saint-Rémy-de-Provence; urban location: Marseille). Hair samples were collected and analyzed to determine the levels of exposure to trace metals. Participants with 'risky' levels were given corresponding advice sheets on how to reduce their exposure or, for certain metals, they were encouraged to find out about potential sources of exposure. A second hair sample was collected and analyzed 3 months later. It was found that 109 women had 'risky' levels of exposure to trace metals, out of a total of 184 women (59.2 %). Cerium was the most frequently identified metal (N = 26), followed by nickel (N = 23), and titanium (N = 19). There were more women at the urban center with 'risky' levels (56/86; 65.1 %) than at the rural center (53/98; 54.1 %), but this difference was not statistically significant (p = 0.13). Advice sheets were given to 64 of the 109 participants with 'risky' levels (58.7 %), but only 21 returned for the second hair analysis. Of these, 14 were found to have reduced their exposure, which corresponds to just 12.8 % (14/109) of the participants with 'risky' levels. These results indicate that it would be helpful to develop new interventions to reduce trace metal exposure during or prior to pregnancy.


Chaetomugilins and Chaetoviridins-Promising Natural Metabolites: Structures, Separation, Characterization, Biosynthesis, Bioactivities, Molecular Docking, and Molecular Dynamics.
Fungi are recognized as luxuriant metabolic artists that generate propitious biometabolites. Historically, fungal metabolites have largely been investigated as leads for various therapeutic agents. Chaetomugilins and the closely related chaetoviridins are fungal metabolites, and each has an oxygenated bicyclic pyranoquinone core. They are mainly produced by various Chaetomaceae species. These metabolites display unique chemical features and diversified bioactivities. The current review gives an overview of research about fungal chaetomugilins and chaetoviridins regarding their structures, separation, characterization, biosynthesis, and bioactivities. Additionally, their antiviral potential towards the SARS-CoV-2 protease was evaluated using docking studies and molecular dynamics (MD) simulations. We report on the docking and predictive binding energy estimations using reported crystal structures of the main protease (PDB ID: 6M2N, 6W81, and 7K0f) at variable resolutions-i.e., 2.20, 1.55, and 1.65 Å, respectively. Chaetovirdin D (43) exhibited highly negative docking scores of -7.944, -8.141, and -6.615 kcal/mol, when complexed with 6M2N, 6W81, and 7K0f, respectively. The reference inhibitors exhibited the following scores: -5.377, -6.995, and -8.159 kcal/mol, when complexed with 6M2N, 6W81, and 7K0f, respectively. By using molecular dynamics simulations, chaetovirdin D's stability in complexes with the viral protease was analyzed, and it was found to be stable over the course of 100 ns.


Epidemiology of late preterm and early term births - An international perspective.
Late preterm (34-36 weeks of gestational age (GA)), and early term (37-38 weeks GA) birth rates among singleton live births vary from 3% to 6% and from 15% to 31%, respectively, across countries, although data from low- and middle-income countries are sparse. Countries with high preterm birth rates are more likely to have high early term birth rates; many risk factors are shared, including pregnancy complications (hypertension, diabetes), medical practices (provider-initiated delivery, assisted reproduction), maternal socio-demographic and lifestyle characteristics and environmental factors. Exceptions include nulliparity and inflammation which increase risks for preterm, but not early term birth. Birth before 39 weeks GA is associated with adverse child health outcomes across a wide range of settings. International rate variations suggest that reductions in early delivery are achievable; implementation of best practice guidelines for obstetrical interventions and public health policies targeting population risk factors could contribute to prevention of both late preterm and early term births.


Restriction endonuclease Bam H I induces chromosomal aberrations in Chinese hamster ovary (CHO) cells.
Treatment of Chinese hamster ovary (CHO) cells with the restriction endonuclease Bam H I (recognition site: G/GATCC) leads to high frequencies of chromosomal aberrations. Experiments with bromodeoxyuridine-labelled chromosomes show that the aberrations occur nearly exclusively in first post-treatment metaphases. The results are interpreted to mean that only some of the cells take up the enzyme and that these cells are the ones showing the aberrations. Cells which do not take up the enzyme show up as differentially stained metaphases and have no aberrations. Why some cells take up the restriction enzyme and others not is not known, possibly this is dependent on the physiological condition of the cells.


Postcoital contraceptive effects of agonist analogs of luteinizing hormone-releasing hormone.
Various analogs of synthetic hypothalamic luteinizing hormone-releasing hormone (LH-RH) were evaluated for agonistic (ovulation-inducing), postcoital contraceptive, and direct uterotrophic activities. All analogs showing agonistic activity also possessed the ability to terminate pregnancy, as did LH-RH; there appeared to be a direct relationship between agonistic and postcoital potency and activity. The highly potent and active LH-RH agonist, D-[Ala]6-des-[Gly]10-pro9-ethylamide-LH-RH, proved to be the most potent and active postcoital preimplantational and postimplantational antifertility agent. In contrast to LH-RH, none of the analogs tested in the hypophysectomized animal produced a uterotrophic effect, revealing a selective extrapituitary effect of the parent hormone. The collective data demonstrate that peptides derived from LH-RH and bearing agonistic properties can terminate pregnancy postcoitally, via disruption of the pituitary-ovarian reproductive complex. Possible mechanisms are discussed, and the use of members of this neurohormonal class as potential profertility agents should be weighed with caution.


Synthesis, characterization and photocatalytic properties of nanostructured lanthanide doped β-NaYF4/TiO2 composite films.
The photocatalytic approach is known to be one of the most promising advanced oxidation processes for the tertiary treatment of polluted water. In this paper, β-NaYF4/TiO2 composite films have been synthetized through a novel sol-gel/spin-coating approach using a mixture of β-diketonate complexes of Na and Y, and Yb3+, Tm3+, Gd3+, Eu3+ as doping ions, together with the TiO2 P25 nanoparticles. The herein pioneering approach represents an easy, straightforward and industrially appealing method for the fabrication of doped β-NaYF4/TiO2 composites. The effect of the doped β-NaYF4 phase on the photocatalytic activity of TiO2 for the degradation of methylene blue (MB) has been deeply investigated. In particular, the upconverting TiO2/β-NaYF4: 20%Yb, 2% Gd, x% Tm (x = 0.5 and 1%) and the downshifting TiO2/β-NaYF4: 10% Eu composite films have been tested on MB degradation both under UV and visible light irradiation. An improvement up to 42.4% in the degradation of MB has been observed for the TiO2/β-NaYF4: 10% Eu system after 240 min of UV irradiation.


Basic characteristics of chronic hypotension cases: a longitudinal follow-up study from 1958 through 1999.
Few epidemiological studies have been conducted on the prevalence, blood pressure trends by age, and basic characteristics of chronic hypotension. Among 13,370 subjects (5,094 men and 8,276 women) examined from 1958 to 1999 in Japan, 92 were identified as chronic hypotensives (11 men and 81 women) whose systolic blood pressure (SBP, mmHg) was lower than 100 mmHg for 8 or more years. Trends of SBP and body mass index (BMI, kg/m2) were determined over a 16-year period in this group of chronic hypotensives and 276 age- and sex-matched controls (33 men and 243 women); during this 16-year period, the chronic hypotensives and controls ranged in age from 19 to 75 years. BMI, heart rate (HR, bpm), body temperature (degrees C), Hb (g/dl), and creatinine (Cre, mg/dl) were compared between the chronic hypotensives and the controls at the last examination. The chronic hypotensives had a female preponderance (0.2% in men and 1.0% in women, p=0.001), and their SBP and BMI increased little with increasing age. BMI (20.2+/-3.4), BMI-adjusted SBP (101+/-19), HR (63+/-10), body temperature (36.7+/-0.3), Hb (12.5+/-1.1), and Cre (0.81+/-0.13) were lower in the chronic hypotensives than those (22.9+/-3.4, 126+/-20, 68+/-10, 36.8+/-0.3, 12.9+/-1.1, and 0.86+/-0.12, respectively) in controls (p<0.05). The present results clearly show that chronic hypotensives have a female preponderance and low BMI, HR, body temperature, Hb, and Cre in addition to low SBP that does not increase with age.


Colorectal cancer metastases affect the biochemical characteristics of the human liver beta-adrenoceptor-G-protein-adenylate cyclase system.
The sympathetic-catecholamine system is involved in the regulation of hepatic metabolic pathways mainly through cAMP-linked beta2-adrenoceptors (beta2-ARs) in humans and to a lesser extent through cAMP-independent mechanisms, but no information is available about the possible biochemical changes of beta2-ARs and their signalling pathways in human colorectal cancer (CRC) and colorectal cancer hepatic metastases (CRCHM). Changes in density and distribution of beta-ARs as well as in post-receptor signalling components were studied in membranes of human liver with CRCHM, and for comparison, in membranes of nonadjacent, non-metastatic human liver (NA-NM) obtained from 13 patients, using binding and competition binding studies. Studies were also carried out using normal and cancerous human colon tissues. In CRCHM, the density of beta-ARs (B(max)) was significantly reduced, compared to NA-NM liver tissues (40.09+/-2.83 vs. 23.09+/-3.24 fmol/mg protein; P<0.001). A similar decrease in the beta-AR density was observed in the colon with primary colorectal cancer compared to healthy colon (37.6+/-2.2 vs. 23.8+/-3.5 fmol/mg protein), whereas the affinity of ICYP binding to the receptor remained unaffected. Desensitized beta-ARs were uncoupled from stimulatory G-protein (G(S)), as total density of beta-adrenoceptors in the high affinity state was significantly reduced. Concomitantly, CRCHM elicited decrease in the catalytic adenylate cyclase (AC) activity (cAMP formation) in response to isoproterenol plus GTP or forskolin or NaF. In NA-NM and CRCHM liver, the inhibition-concentration curves of ICI 118.551 showed the presence of a homogeneous population of the beta2-AR subtypes. Neither the binding patterns nor the inhibition constant (K(i)) of ICI 118.551 were altered in CRCHM. In CRCHM, the hepatic beta-AR-G-protein(s)-AC signalling system was markedly impaired, thus, these changes may well influence beta-AR-mediated functions in both organs.


Effect of 5-HMF and furfural additives on bio-hydrogen production by photo-fermentation from giant reed.
Substances harmful to photo-fermentative biological hydrogen production (PFHP) were produced during cellulose hydrolysis. This study aimed to evaluate the effect of by-products (5-hydroxymethylfurfural (5-HMF) and furfural) released from lignocellulose during enzymatic hydrolysis process on PFHP. The exist of 5-HMF inhibited the hydrogen production. However, 0.2 g/L furfural improved the hydrogen production by 19 % compared to no addition (511.6 mL) with a maximum concentration of nitrogenase (109.96 IU/L) at 96 h. Furthermore, a 18.7 % enhancement of hydrogen production was also observed when 0.2 g/L 5-HMF and furfural were mixed at a ratio of 1:1, while decrement of hydrogen production at higher addition was observed as well. Through the scatter matrix analysis, it was concluded that 5-HMF and furfural additives had significant effects on PFHP. This study gave an insight into effect of lignocellulosic by-products on biohydrogen production.


Organoids: A new approach in toxicity testing of nanotherapeutics.
Nanotechnology has revolutionized diverse fields, which include agriculture, the consumer market, medicine, and other fields. Widespread use of nanotechnology-based products has led to increased prevalence of these novel formulations in the environment, which has raised concerns regarding their deleterious effects. The application of nanotechnology-based formulations into clinical use is hampered by the lack of the availability of effective in vitro systems, which could accurately assess their in vivo toxic effects. A plethora of studies has shown the hazardous effects of nanoparticle-based formulations in two-dimensional in vitro cell cultures and animal models. These have some associated disadvantages when used for the evaluation of nano-toxicity. Organoid technology fills the space between existing two-dimensional cell line culture and in vivo models. The uniqueness of organoids over other systems for evaluating toxicity caused by nano-drug formulation includes them being a co-culture of diverse cell types, dynamic flow within them that simulates the actual flow of nanoparticles within biological systems, extensive cell-cell, cell-matrix interactions, and a tissue-like morphology. Thus, it mimics the actual tissue microenvironment and, subsequently, provides an opportunity to study drug metabolism and toxico-dynamics of nanotechnology-based novel formulations. The use of organoids in the evaluation of nano-drug toxicity is in its infancy. A limited number of studies conducted so far have shown good predictive value and efficiently significant data correlation with the clinical trials. In this review, we attempt to introduce organoids of the liver, lungs, brain, kidney intestine, and potential applications to evaluate toxicity caused by nanoparticles.


Base catalyzed multicomponent synthesis of spiroheterocycles with fused heterosystems.
Structurally diverse spiroheterocycles incorporating medicinally privileged heterosystems have been synthesized by a simple and convenient synthesis involving triethylamine catalyzed multicomponent domino reaction of 2-aminobenzothiazoles with isatin and cyclic 1,3-diketones.


Eosinophilic gastritis in children: clinicopathological correlation, disease course, and response to therapy.
Eosinophilic gastritis (EG), defined by histological criteria as marked eosinophilia in the stomach, is rare, and large studies in children are lacking. We sought to describe the clinical, endoscopic, and histopathological features of EG, assess for any concurrent eosinophilia at other sites of the gastrointestinal (GI) tract, and evaluate response to dietary and pharmacological therapies. Pathology files at our medical center were searched for histological eosinophilic gastritis (HEG) with ≥70 gastric eosinophils per high-power field in children from 2005 to 2011. Pathology slides were evaluated for concurrent eosinophilia in the esophagus, duodenum, and colon. Medical records were reviewed for demographic characteristics, symptoms, endoscopic findings, comorbidities, and response to therapy. Thirty children with severe gastric eosinophilia were identified, median age 7.5 years, 14 of whom had both eosinophilia limited to the stomach and clinical symptoms, fulfilling the clinicopathological definition of EG. Symptoms and endoscopic features were highly variable. History of atopy and food allergies was common. A total of 22% had protein-losing enteropathy (PLE). Gastric eosinophilia was limited to the fundus in two patients. Many patients had associated eosinophilic esophagitis (EoE, 43%) and 21% had eosinophilic enteritis. Response to dietary restriction therapy was high (82% clinical response and 78% histological response). Six out of sixteen patients had persistent EoE despite resolution of their gastric eosinophilia; two children with persistent HEG post therapy developed de novo concurrent EoE. HEG in children can be present in the antrum and/or fundus. Symptoms and endoscopic findings vary, highlighting the importance of biopsies for diagnosis. HEG is associated with PLE, and with eosinophilia elsewhere in the GI tract including the esophagus. The disease is highly responsive to dietary restriction therapies in children, implicating an allergic etiology. Associated EoE is more resistant to therapy.


Conversion of phosphoglycolate to phosphate termini on 3' overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1.
Mammalian cells contain potent activity for removal of 3'-phosphoglycolates from single-stranded oligomers and from 3' overhangs of DNA double strand breaks, but no specific enzyme has been implicated in such removal. Fractionated human whole-cell extracts contained an activity, which in the presence of EDTA, catalyzed removal of glycolate from phosphoglycolate at a single-stranded 3' terminus to leave a 3'-phosphate, reminiscent of the human tyrosyl-DNA phosphodiesterase hTdp1. Recombinant hTdp1, as well as Saccharomyces cerevisiae Tdp1, catalyzed similar removal of glycolate, although less efficiently than removal of tyrosine. Moreover, glycolate-removing activity could be immunodepleted from the fractionated extracts by antiserum to hTdp1. When a plasmid containing a double strand break with a 3'-phosphoglycolate on a 3-base 3' overhang was incubated in human cell extracts, phosphoglycolate processing proceeded rapidly for the first few minutes but then slowed dramatically, suggesting that the single-stranded overhangs gradually became sequestered and inaccessible to hTdp1. The results suggest a role for hTdp1 in repair of free radical-mediated DNA double strand breaks bearing terminally blocked 3' overhangs.


Effects of testosterone on the behavior of male cynomolgus monkeys (Macaca fascicularis).
To determine the threshold doses of testosterone propionate (TP) that cause clear-cut behavioral changes in the sexual behavior of castrated male cynomolgus monkeys, observations were made on three males during successive 5-week treatment periods while they received daily subcutaneous doses of 100 micrograms TP increasing in octaves to 25.6 mg TP. Males were tested with each of the same two ovariectomized, estrogen-treated females (6 pairs, 330 1-hr behavior tests). To mimic the diurnal plasma testosterone rhythm, TP injections were given at 1600 hr and blood samples were obtained at 0800 hr (141 samples). Male ejaculatory activity increased at the threshold dose of 200 micrograms TP per day giving plasma testosterone levels of 830 ng/100 ml, which is in the physiological range of 600-1600 ng/100 ml for intact males. This threshold dose was eight times higher than in rhesus monkeys on a dose per kilogram body weight basis. There was a further marked increase in ejaculatory performance at higher doses (6.4 to 25.6 mg) giving supraphysiological plasma levels of 4000-9000 ng/100 ml. There were individual differences in the behavioral changes occurring with TP treatment, and the female partner modulated the effects. These findings were generally similar to those obtained with male rhesus monkeys, but certain species differences were noted.


Anidoxime: a clinical trial of an oral analgesic agent.
The new oral analgesic drug anidoxime was compared with dihydrocodeine. There were no side-effects, and no significant differences between the effects of dihydrocodeine 50 mg, anidoxime 75 mg or anidoxime 100 mg.


Fecal incontinence: an up-to-date critical overview of surgical treatment options.
Surgery is the last resort for patients suffering from severe fecal incontinence. The armamentarium of surgical options for this condition has increased impressively during the last decade. Nevertheless, this fact seems to make neither patients nor surgeons feel more comfortable. Treatment of fecal incontinence still remains a challenge to modern medicine due to many specific sides of this problem. This article gives an up-to-date overview of existing operative treatment options. An unbiased review of relevant literature was performed to assess the role of all methods of surgical treatment for fecal incontinence available nowadays. Recent studies have shown poor late results after primary sphincter repair and low predictive value for most preoperative diagnostic tests. New surgical options such as artificial devices and electrically stimulated muscle transpositions are doomed by low success rates and unacceptably frequent complications. That is why current attention has focused on non- or minimally invasive therapies such as sacral nerve stimulation and temperature-controlled radio-frequency energy delivery to the anal canal. However, all these innovative techniques remain experimental till enough high-evidence data are gathered for their objective evaluation. Careful and detailed preoperative assessment to exactly determine the etiology of incontinence and individual approach remain the cornerstones of surgical treatment of fecal incontinence nowadays.


The latent structure of depressive symptoms across clinical high risk and chronic phases of psychotic illness.
Depressive symptoms are highly prevalent in psychotic populations and result in significant functional impairment. Limited knowledge of whether depressive symptoms are invariant across stages of illness curtails our ability to understand how these relate to illness progression. Clarifying the latent structure of depressive symptoms across stages of illness progression would aid etiological conceptualizations and preventive models. In the present study, one-factor (including all items) and two-factor (depression/hopelessness and guilt/self-depreciation) solutions were specified through confirmatory factor analysis (CFA). Measurement invariance analyses were undertaken across schizophrenia (SCZ; n = 312) and clinical high-risk (CHR; n = 175) groups to estimate whether the same construct is being measured across groups. Clinical correlates of the factors were examined. Results indicated that CHR individuals had a greater proportion of mood disorder diagnoses. Metric invariance held for the one-factor solution, and scalar invariance held for the two-factor solution. Notably, negative symptoms did not correlate with depressive symptoms in the SCZ group, though strong correlations were observed in CHR individuals. Positive symptoms were comparably associated with depressive symptoms in both groups. Results suggest depressive symptoms are more prevalent in CHR individuals. Targeting these symptoms may aid future efforts to identify risk of conversion. Further, some depressive symptoms may be systematically more endorsed in CHR individuals. Separating into depression/hopelessness and guilt/self-depreciation scores may aid comparability across stages of illness progression, though this issue deserves careful attention and future study.


Cell density, negative proliferation control, and phosphorylation of retinoblastoma protein.
Cell density negative control (CDNC) of normal human fibroblast proliferation occurs after stimulation by mitogens with different signal transduction mechanism. Delayed exposure to agents that interfere with CDNC, such as double-stranded RNA and vanadate, reveals the existence of a biochemical event, involved in CDNC, that occurs 5-8 hr after the beginning of mitogenic stimulation. This is earlier than the point of "mitogenic commitment," defined by the duration of mitogen exposure required for cell cycle entry (8-18 hr). Phosphorylation of the retinoblastoma gene product (pRB) begins 8-10 hr after mitogen stimulation and is nearly complete at 18 hr, just as the first cells enter S-phase. CDNC prevents pRB phosphorylation. Interferon beta delays pRB phosphorylation by up to 20 hr but has little effect on the timing of mitogenic commitment. Thus mitogenic commitment is located in time between CDNC and pRB phosphorylation. When agents that cause a release from CDNC are applied to dense, negatively controlled cultures after 18 hr of EGF stimulation, pRB phosphorylation occurs 6-8 hr after release. This suggests that the negatively controlled cells process the mitogenic signal but accumulate at a restriction point. The relatively early timing of CDNC-related events in the prereplicative phase raises the possibility that pRB phosphorylation is a consequence rather than a prerequisite for release from cell density negative control.


A glass forming module for organic molecules: making tetraphenylporphyrin lose its crystallinity.
Formation of stable glassy phases can be induced through rational design in compounds which otherwise readily crystallize, such as tetraphenylporphyrin, by simple functionalization with moieties known to promote glass formation such as mexylaminotriazine units.


Oral contraceptives and cycle control: a critical review of the literature.
Control of spotting and breakthrough bleeding and absence of withdrawal bleeding, collectively termed cycle control, is the single most important determinant of whether a new user of oral contraceptives (OCs) will continue this method. However, information about different OC preparations and how they affect such problems, including the effects of progestogen and estrogen phasing and the components of these hormones, is scant and confusing. Studies cited in this report reveal highly variable rates of bleeding problems in women taking OCs: after 6 months of OC use, the prevalence of spotting varied between 0% and 8.5%; of breakthrough bleeding, 0% and 12.2%; and of amenorrhea, 0% and 5.8%. At least some of this variation is attributable to differing study populations and cultures, study designs, and the manner in which data were collected and reported. However, methodologic weaknesses were common, often involving lack of randomization and blinding, and attrition rates were high. Despite these limitations, it is clear that the frequency of bleeding problems decreases with continuing use of OCs, emphasizing the need for patient reassurance about the transient nature of these problems. In addition, gestodene-containing preparations appear to offer better cycle control than do desogestrel-containing preparations and levonorgestrel-containing preparations better control than norethindrone-containing preparations. However, the strongest lesson to emerge is the need for more rigorous studies to adequately address questions of comparative bleeding problems, particularly with newer triphasic formulations. These conclusions underscore the importance of counseling new OC users about the possibility of bleeding problems, reassuring them that most such problems are temporary, and, that if compliance is maintained, these will not impair contraceptive efficacy.


Lipopolysaccharide stimulates the production of prostaglandin E2 and the receptor Ep4 in osteoblasts.
Previous studies have indicated that one of the causes of alveolar bone destruction with periodontitis is lipopolysaccharide (LPS) from the cell wall of gram-negative bacteria in plaque, and that prostaglandin E(2) (PGE(2)) is one of the bone resorption factors that stimulate osteoclast formation through an intercellular interaction between osteoblasts and osteoclast precursors. The present study was undertaken to determine the effect of LPS on cell growth, alkaline phosphatase (ALPase) activity, the production of PGE(2), and the expression of receptors by PGE(2), cyclooxygenase (COX)-1, and COX-2, using human osteosarcoma cell line Saos-2 as osteoblasts. The cells were cultured with 0, 1, or 10 microg mL(-1) of LPS for up to 14 days. The production of PGE(2) and the gene expression of COX-1, COX-2, and PGE(2) receptors, including Ep1, Ep2, Ep3, and Ep4, were determined using enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription-polymerase chain reaction (real-time RT-PCR), respectively. With the addition of LPS, cell growth and ALPase activity decreased by day 5 of the culture, while PGE(2) production increased in a dose-dependent manner throughout the entire 14-day culture period. LPS-reduced ALP activity and LPS-induced PGE(2) production returned to the control level by the addition simultaneously with indomethacin. The expression of COX-1, Ep1, Ep2, and Ep3 receptors decreased on day 14 of the culture, whereas the expression of COX-2 and Ep4 receptors increased significantly with the addition of LPS. These results suggest that LPS promotes PGE(2) production by increasing the expression of COX-2, and that LPS promotes the production of Ep4 receptors in osteoblasts. These results also indicate that LPS-induced PGE(2) may combine with osteoblast Ep4 receptors in autocrine or paracrine modes, and may promote the formation of osteoclasts.


The effect of folic acid deficiency on FGF pathway via Brachyury regulation in neural tube defects.
Folate deficiency in early development leads to disturbance in multiple processes, including neurogenesis during which fibroblast growth factor (FGF) pathway is one of the crucial pathways. Whether folic acid (FA) directly affects FGF pathways to influence neurodevelopment and the possible mechanism remains unclear. In this study, we presented evidence that in human FA-insufficient encephalocele, the FGF pathway was interfered. Furthermore, in Brachyury knockout mice devoid of such T-box transcription factors regulating embryonic neuromesodermal bipotency and a key component of FGF pathway, change in expression of Brachyury downstream targets, activator Fgf8 and suppressor dual specificity phosphatase 6 was detected, along with the reduction in expression of other key FGF pathway genes. By using a FA-deficient cell model, we further demonstrated that decrease in Brachyury expression was through alteration in hypermethylation at the Brachyury promoter region under FA deficiency conditions, and suppression of Brachyury promoted the inactivation of the FGF pathway. Correspondingly, FA supplementation partially reverses the effects seen in FA-deficient embryoid bodies. Lastly, in mice with maternal folate-deficient diets, aberrant FGF pathway activity was found in fetal brain dysplasia. Taken together, our findings highlight the effect of FA on FGF pathways during neurogenesis, and the mechanism may be due to the low expression of Brachyury gene via hypermethylation under FA-insufficient conditions.-Chang, S., Lu, X., Wang, S., Wang, Z., Huo, J., Huang, J., Shangguan, S., Li, S., Zou, J., Bao, Y., Guo, J., Wang, F., Niu, B., Zhang, T., Qiu, Z., Wu, J., Wang, L. The effect of folic acid deficiency on FGF pathway via Brachyury regulation in neural tube defects.


Raman spectroscopy for the analysis of different exo-polysaccharides produced by bacteria.
In this study, Raman spectroscopy is employed for the characterization and comparison of two different classes of exo-polysaccharides including glucans and fructans which are produced by different bacteria. For this purpose, nine samples are used including five samples of glucans and four of fructans. Raman spectral results of all these polysaccharides show clear differences among various glucans as well as fructans showing the potential of this technique to identify the differences within the same class of the compounds. Moreover, these two classes are also compared on the basis of their Raman spectral data and can be differentiated on the basis of their unique Raman features. Multivariate data analysis techniques, Principle Component Analysis (PCA) is found very helpful for the comparison of the Raman spectral data of these classes of the carbohydrates.


Nanostructured sensor platform based on organic polymer conjugated to metallic nanoparticle for the impedimetric detection of SARS-CoV-2 at various stages of viral infection.
The projection of new biosensing technologies for genetic identification of SARS-COV-2 is essential in the face of a pandemic scenario. For this reason, the current research aims to develop a label-free flexible biodevice applicable to COVID-19. A nanostructured platform made of polypyrrole (PPy) and gold nanoparticles (GNP) was designed for interfacing the electrochemical signal in miniaturized electrodes of tin-doped indium oxide (ITO). Oligonucleotide primer was chemically immobilized on the flexible transducers for the biorecognition of the nucleocapsid protein (N) gene. Methodological protocols based on cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and atomic force microscopy (AFM) were used to characterize the nanotechnological apparatus. The biosensor's electrochemical performance was evaluated using the SARS-CoV-2 genome and biological samples of cDNA from patients infected with retrovirus at various disease stages. It is inferred that the analytical tool was able to distinguish the expression of SARS-CoV-2 in patients diagnosed with COVID-19 in the early, intermediate and late stages. The biosensor exhibited high selectivity by not recognizing the biological target in samples from patients not infected with SARS-CoV-2. The proposed sensor obtained a linear response range estimated from 800 to 4000 copies µL-1 with a regression coefficient of 0.99, and a detection limit of 258.01 copies µL-1. Therefore, the electrochemical biosensor based on flexible electrode technology represents a promising trend for sensitive molecular analysis of etiologic agent with fast and simple operationalization. In addition to early genetic diagnosis, the biomolecular assay may help to monitor the progression of COVID-19 infection in a novel manner.


Design and bioevaluation of a 32P-patch for brachytherapy of skin diseases.
The purpose of this study was to design and evaluate a 32P patch for brachytherapy of skin diseases. We employed Phosphoric-32P-acid and Chromic 32P-phosphate in combination with natural rubber or silicone to produce the patches. Stability studies in vitro to evaluate the leakage of radioactivity, autoradiographic studies to evaluate homogeneity and shielding, as well as therapeutic efficacy in an animal model of skin cancer of the selected 32P patch were performed. The 32P-silicone-patch demonstrated its safety for external application. Tumor growth was arrest and complete regressions of tumors were seen in some other cases with 40 Gy applied in a single-dose scheme. In conclusion, the 32P-silicone-patch is easy to prepare and use in the treatment of skin diseases.


Transitions in neural oscillations reflect prediction errors generated in audiovisual speech.
According to the predictive coding theory, top-down predictions are conveyed by backward connections and prediction errors are propagated forward across the cortical hierarchy. Using MEG in humans, we show that violating multisensory predictions causes a fundamental and qualitative change in both the frequency and spatial distribution of cortical activity. When visual speech input correctly predicted auditory speech signals, a slow delta regime (3-4 Hz) developed in higher-order speech areas. In contrast, when auditory signals invalidated predictions inferred from vision, a low-beta (14-15 Hz) / high-gamma (60-80 Hz) coupling regime appeared locally in a multisensory area (area STS). This frequency shift in oscillatory responses scaled with the degree of audio-visual congruence and was accompanied by increased gamma activity in lower sensory regions. These findings are consistent with the notion that bottom-up prediction errors are communicated in predominantly high (gamma) frequency ranges, whereas top-down predictions are mediated by slower (beta) frequencies.


Neoaortic bicuspid valve in arterial switch operation: mid-term follow-up.
We sought to identify the prevalence of bicuspid pulmonary valve among patients with transposition of the great arteries undergoing the arterial switch operation and evaluate functional integrity of that valve in the neoaortic position. Between October 1985 and December 2001, 391 patients had an arterial switch operation for transposition and its variants. Perioperative information and follow-up data were available for 342 patients. The serial echocardiograms of patients with bicuspid pulmonary valve were reviewed. The neoaortic valve was serially assessed, focusing on aortic insufficiency, annulus diameter, and pressure gradients. Twenty-four patients (7%) had a bicuspid pulmonary valve. Age at operation was 5 days to 12 years. Two patients were lost to follow up, and 22 patients had mean follow-up of 5.3 years (range, 2 months to 13 years), of which 21 patients were alive and 1 died late. At least two postoperative echocardiogram reports were available on 19 patients. Seven patients had no neoaortic regurgitation, and 10 had trivial regurgitation. Severe aortic regurgitation developed in 1 patient with endocarditis and in another with repair of Taussig-Bing anomaly. Neoaortic valve size indexed to body surface area showed an increase in annular diameter over time proportional to somatic growth. No significant valve stenosis developed. Encountering a bicuspid pulmonary valve at the time of an arterial switch operation is not uncommon. The integrity of a bicuspid pulmonary valve in the neoaortic position is maintained at a mean follow-up of 5.3 years. We believe that the presence of a bicuspid pulmonary valve is not a contraindication to an arterial switch operation.


Elucidating the molecular mechanism of PAMAM-siRNA dendriplex self-assembly: effect of dendrimer charge density.
Dendrimers are attractive vehicles for nucleic acid delivery due to monodispersity and ease of chemical design. The purpose of this study was to elucidate the self-assembly process between small interfering RNA (siRNA) and different generation poly(amidoamine) dendrimers and to characterize the resulting structures. The generation 4 (G4) and G7 displayed equal efficiencies for dendriplex aggregate formation, whereas G1 lacked this ability. Nanoparticle tracking analysis and dynamic light scattering showed reduced average size and increased polydispersity at higher dendrimer concentration. The nanoparticle tracking analysis indicated that electrostatic complexation results in an equilibrium between differently sized complex aggregates, where the centre of mass depends on the siRNA:dendrimer ratio. Isothermal titration calorimetric data suggested a simple binding for G1, whereas a biphasic binding was evident for G4 and G7 with an initial exothermic binding and a secondary endothermic formation of larger dendriplex aggregates, followed by agglomeration. The initial binding became increasingly exothermic as the generation increased, and the values were closely predicted by molecular dynamics simulations, which also demonstrated a generation dependent differences in the entropy of binding. The flexible G1 displayed the highest entropic penalty followed by the rigid G7, making the intermediate G4 the most suitable for dendriplex formation, showing favorable charge density for siRNA binding.


[Initial experience of a series of robotic-assisted laparoscopic adrenalectomy].
We present our initial experience using robotic-assisted laparoscopic adrenalectomy in the surgical treatment of adrenal masses. A total of 18 patients (11 women and 7 men) diagnosed of a functioning or non-functioning adrenal tumor mass were operated on in our facilities between October 2009 and October 2011. Surgical variables, intra-hospital recovery time, pathological findings and peri- and post-operatory findings were evaluated. Mean age of the population intervened was 51.2 years (range 18-81), average ASA score 2.11 (range 1-4) and BMI 27.0 (range 18.8-36.1). Of the 18 patients, 11 were operated on the left side and 7 on the right. Mean surgery time was 150 (range 84-329) min and intra-operatory bleeding 121 (range 10-1500) ml, with a mean loss of hemoglobin and hematocrits of 2.11g/dl and 6.33%, respectively. Two patients were converted to conventional surgery. The factors influencing surgical conversion were: normal size (>10cm), tumor weight (>100g.), active pheochromocytoma and left localization of the tumor. Seven functioning cortical adenomas, 6 metastatic adrenal tumors, 3 pheochromocytoma and 2 incidental tumors were excised. Mean tumor size was 5.39 (range 3-15) cm. Median hospital stay was 6 days (range 4-14). Five patients had peri-operatory complication. Of these, only one (5%) had major complications (Clavien III). Mean follow-up was 6 months (range 2-24). Robotic technology for laparoscopic adrenalectomies is a valid option for adrenal tumor treatment. In our experience with a relatively short learning curve, it makes it possible to reduce hospital treatment times and the intra- and post-operatory complications, without affecting the oncological and post-operatory functional results.


[Various morphofunctional characteristics of hematopoietic tissue in preleukemic conditions].
Cultural, ultrastructural, cytochemical and histological investigations of bone marrow tissue were conducted in 26 patients with varying types of preleukemia states. A number of early structural, morphological and functional signs of hemopoietic disorders of different character and manifestation degree have been revealed. Particularly, a relationship has been established between the pathologic changes appearing in the bone marrow stroma and disorders in the morphological and functional state of the hemopoietic cells.


Interaction of a transcriptional activator, OmpR, with reciprocally osmoregulated genes, ompF and ompC, of Escherichia coli.
The ompB locus, comprised of the genes ompR and envZ, regulates the expression of the genes ompF and ompC that encode the major porin proteins in the outer membrane of Escherichia coli K-12. OmpR is believed to activate transcription of ompF and ompC in a reciprocal manner depending upon the osmolarity of the culture medium. We were able to purify OmpR to homogeneity and to characterize its interaction with the porin gene promoters. The purified OmpR was shown to bind specifically to promoter fragments of both ompF and ompC. Deoxyribonuclease I footprinting was carried out in order to determine binding sites of OmpR in the promoter regions of the ompF and ompC. OmpR was found to protect the regions -105 to -60 of ompF and -102 to -78 of ompC, respectively. Two consensus sequences were found in these protected sites and are likely to play an important role in OmpR recognition of these promoter regions. The purified OmpR was also shown to be functionally active in transcription in vitro; OmpR activates the expression of ompF and inhibits the transcription of ompC from the most distal of its three tandem promoters, P3.


Ciprofloxacin-induced torsade de pointes.
A 65-year-old man with recently diagnosed urinary tract infection treated with ciprofloxacin (Cipro) presented to our institution with recurrent seizure-like activity. His rhythm revealed torsade de pointes, which required defibrillation. Subsequent electrocardiogram revealed severely prolonged QT interval, which near-completely resolved 7 days later off Cipro. This case highlights a rare but potentially fatal side effect of quinolone antibiotics, especially in combination with other QT-prolonging medications. Review of the literature with regard to prevalence, mechanism, and assessment and treatment of this potentially fatal incidence is provided.


Corticosterone in the dorsolateral striatum facilitates the extinction of stimulus-response memory.
Glucocorticoid hormones are crucially involved in modulating mnemonic processing of stressful or emotionally arousing experiences. They are known to enhance the consolidation of new memories, including those that extinguish older memories. In this study, we investigated whether glucocorticoids facilitate the extinction of a striatum-dependent, and behaviorally more rigid, stimulus-response memory. For this, male rats were initially trained for six days on a stimulus-response task in a T-maze to obtain a reward after making an egocentric right-turn body response, regardless of the starting position in this maze. This training phase was followed by three extinction sessions in which right-turn body responses were not reinforced. Corticosterone administration into the dorsolateral region of the striatum after the first extinction session dose-dependently enhanced the consolidation of extinction memory: Rats administered the higher dose of corticosterone (30 ng), but not lower doses (5 or 10 ng), exhibited significantly fewer right-turn body responses and had longer latencies compared to vehicle-treated animals on the second and third extinction sessions. Co-administration of the glucocorticoid receptor antagonist RU 486 (10 ng) prevented the corticosterone effect, indicating that glucocorticoids enhance the extinction of stimulus-response memory via activation of the glucocorticoid receptor. Corticosterone administration into the dorsomedial striatum did not affect extinction memory. These findings indicate that stress-response mechanisms involving corticosterone actions in the dorsolateral striatum facilitate the extinction of stimulus-response memory that might allow for the development of an opportune behavioral strategy.


Nature visits during the COVID-19 pandemic in Norway: Facilitators, motives, and associations with sociodemographic characteristics.
The COVID-19 pandemic has been linked to increased mental health issues and reduced well-being. Researchers also reports increased frequency of nature visits during the pandemic, proposing it may mitigate some of these negative consequences. Using the case of Norway, a country with ample access to nature and relatively low levels of pandemic-related restrictions, this study sought to (i) understand how the COVID-19 crisis impacted patterns of nature visits and specific nature-based activities, (ii) examine how these patterns varied among different population groups and levels of restrictions, and (iii) explore the motives and facilitators for increased frequency of nature visits. The data were retrieved from a national cross-sectional survey conducted in June 2021, which was designed to assess participants (n = 1,005, age > 15 years) habits in relation to nature visits and outdoor recreation since the beginning of the COVID-19 crisis, and associated factors. The results showed that 32 % of participants increased their frequency of nature visits during the crisis, while 11 % experienced a decrease. Multivariate logistic regression revealed significant positive associations between increased frequency of nature visits and longer duration of lockdown restrictions (OR [95% CI] = 2.35 [1.28-4.29] and 4.92 [2.77-8.74] for a few weeks and several months of lockdown, respectively). Increased frequency of nature visits was also more likely among women, younger respondents, and individuals from high-income households. A Cochran's Q test showed that the most common motive for increased frequency of nature visits was "To be physically active" (74%). The most commonly reported facilitators were the possibility of using natural environments as an alternative to gyms and organized sports alongside having more time available (58 and 49%, respectively). These findings suggest that nature visits provided important opportunities for physical activity during the COVID-19 crisis, but also that the mental health benefits of nature visits during such times may be under-communicated. This highlights the importance of access to natural environments to promote physical activity and health, but also suggests that campaigns that specifically communicate the beneficial effects of nature visits during lockdowns or similar stressful situations might help people cope with the situation.


Anti-fouling and protein separation of PVDF-g-PMAA@MnO2 filtration membrane with in-situ grown MnO2 nanorods.
MnO2 nanorods with controllable scale were grown in the PVDF-g-PMAA modified membrane to form PVDF-g-PMAA@ MnO2 membrane through the in situ redox reaction of KMnO4 solution, which is confirmed by scanning electron microscopy (SEM) and X-ray energy-dispersion spectroscopy (EDX). The pore size of the membrane decreased with the increase of KMnO4 solution concentration. The thermodynamic stability and the hydrophilicity of the membrane were also enhanced by the MnO2 nanorods. The water flux, bovine serum albumin (BSA)/Lysozyme protein solution flux and rejection, flux recovery, etc. showed effective improvement of the anti-fouling performance of the PVDF-g-PMAA@ MnO2 membrane. More importantly, it can effectively separate BSA from lysozyme, which provided a potential application in the field of biology, food, and other industrial fields for the requirement of separation and purification.


Distribution analysis of single nucleotide polymorphisms related to feet and legs and their association with lameness in Vrindavani cattle.
Lameness is one of the most serious economic problems in dairy animals. The present study was undertaken to identify the SNPs associated with lameness in Vrindavani, a synthetic crossbred cattle developed in India. A total of 187 cows were screened for lameness at Cattle and Buffalo Farm, Indian Veterinary Research Institute, Izatnagar, India and 16.04% prevalence was noticed. The effect of age, body weight, parity, and peak yield was not significant on lameness score. Heritability estimate of lameness score was low (0.07 ± 0.01). A total of 90 Vrindavani cows were genotyped by PCR-RFLP for 10 SNPs that were reported to have association with feet and legs in cattle. Five SNPs displayed significant departure from Hardy Weinberg equilibrium. Varying levels of heterozygosity, polymorphic information content, and allelic diversity were noticed at different SNPs. Odds ratio and least squares analysis revealed a significant association (P < 0.05) of three SNPs with lameness in the herd. Cows with AG, TT, and GG genotypes respectively at rs41632254, rs41603160, and rs41636945 loci were less prone to lameness. These genetic markers would certainly aid in development of an early detection system for lameness.


Cunning plasmid fusion mediates antibiotic resistance genes represented by ESBLs encoding genes transfer in foodborne Salmonella.
Foodborne disease caused by antibiotic resistant Salmonella is quite difficult to deal with. In order to further explore the antibiotic resistance associated with gene transfer among foodborne Salmonella, several wild-type Salmonella strains were used as donors and recipients, respectively, to investigate how extended spectrum β-lactamases (ESBLs) encoding genes co-transfer with transposable elements to transmit antibiotic resistance. Antibiotic susceptibility was determined by agar dilution method, the transposase encoding gene was detected via PCR combined with DNA sequencing, S1 nuclease and pulsed field gel electrophoresis (S1-PFGE), and southern-blot. Illumina HiSeq 4000 platform and Nanopore MinION long-read sequencing technology were used to determine the antibiotic resistance encoding genes (ARGs) and their surrounding gene environment. The results indicated that the conjugation frequency was from ×10-4 to ×10-5 per recipient cell. A 185,608-bp-long DNA fragment and two short backbone protein encoding regions in pG19 in the donor fused with part genes in pS3 in the recipient during conjugation, the size of this fusion plasmid is as same as that of pG19. Cefoxitin resistance of the transconjugant was mediated by a tnpA21-related blaDHA-1 transfer. Resistance of Salmonella to ceftriaxone, cefoperazone and ceftiofur was mediated by a tnpU1548 related blaTEM-1B and blaCTX-M-3 transfer. The study indicated that transposase synergy and plasmid selective fusion act as important roles for foodborne Salmonella gathering ARGs. The consistent size of the plasmid before and after fusion suggested the invisibility and complexity of bacterial conjugation without DNA sequencing, the fact reminded us that the rampant transmission of antibiotic-resistance encoding genes would pose tremendous threat to food safety.


A mesoderm-inducing factor from a Xenopus laevis cell line : Chemical properties and relation to the vegetalizing factor from chicken embryos.
We have compared the chemical properties and biological activities of the mesoderm-inducing factor that is secreted by the Xenopus XTC cell line with the vegetalizing factor from chicken embryos. The inducing activity of the factors was tested in different concentrations on totipotent ectoderm either by implantation into early gastrulae of Triturm alpestris or by application of solutions to isolated ectoderm of early gastrulae of Xenopus laevis. Both factors have similar properties. They are not irreversibly inactivated after treatment with 6 M urea or with phenol at 60° C. Reduction with thioglycolic acid inactivates the factors completely. The inducing activity of XTC-conditioned medium decreases only slightly after treatment with 50% formic acid. The apparent molecular mass and the isoelectric point of the factors are similar. The XTC factor was partially purified by size-exclusion and reversed-phase high-pressure liquid chromatography and by isoelectric focusing. The possible relationship of these factors to transforming growth factor β is discussed.


Engineered biosynthesis of novel polyketides: evidence for temporal, but not regiospecific, control of cyclization of an aromatic polyketide precursor.
Aromatic polyketide synthases (PKSs) catalyze the formation and cyclization of polyketide chains of variable lengths, generating a family of compounds of proven medical significance. Initial control over the regiospecificity of cyclization is believed to be exercised by the minimal PKS, composed of the three essential components for polyketide biosynthesis, which catalyzes an intramolecular aldol condensation towards the middle of the chain. Subsequent cyclization reactions are either catalyzed by additional components of the PKS, or occur in the absence of specific catalysts. Structural and biosynthetic studies on SEK4b, a novel octaketide product of a minimal PKS, revealed an unusual cyclization pattern. The first cyclization (an aldol condensation) occurs at the methyl end of the unreduced polyketide backbone precursor. This is followed by hemiketal formation and lactonization. The overall structure of SEK4b is similar to that of SEK4, a previously-identified product of the same genetically-engineered strain, differing only in the positions of a methyl and a pyrone group around a common fused-ring system. The biosynthetic pathways of the two molecules are quite different, however. The yield of SEK4b relative to SEK4 is much higher in the absence of PKS components (aromatases and cyclases) acting later in the pathway. In this cyclization pathway, the regiospecificity of cyclization is not directly controlled by the minimal PKS. Instead, we propose that the enzyme influences cyclization by controlling the timing of chain release. Chain release and cyclization may be concurrent with synthesis. Other PKS subunits appear to stabilize the complex of the PKS with the nascent chain, preventing premature release.


Effect of sleep deprivation on neuroendocrine response to a serotonergic probe in healthy male subjects.
Neuroendocrine responses to stimulation with a selective serotonin reuptake inhibitor (citalopram) were measured to investigate the effects of all-night sleep deprivation on serotonergic function in healthy male subjects (n = 7). We studied citalopram-stimulated prolactin and cortisol plasma concentrations in a placebo-controlled cross-over protocol following sleep and sleep deprivation. Citalopram infusion (20 mg i.v. at 14:20-14:50 h) after a night of undisturbed sleep prompted robust increases in both plasma prolactin and cortisol concentrations. Following a night of sleep deprivation, by contrast, the citalopram-induced prolactin response was blunted, but the cortisol response was not significantly altered. This differential response pattern relates to the distinct pathways through which serotonin may activate the corticotrophic and the lactotrophic systems. While an unchanged cortisol response does not indicate (but also does not refute the possibility of) an altered serotonergic responsivity following sleep deprivation, the suppressed prolactin response could reflect a downregulation of 5-HT1A or 2 receptors. An alternative, not mutually exclusive, explanation points to the possibility that sleep deprivation activates the tubuloinfundibular dopaminergic system, the final inhibitory pathway of prolactin regulation.


A labeled data set of underwater images of fish and crab species from five mesohabitats in Puget Sound WA USA.
The sustainable management of fisheries and aquaculture requires an understanding of how these activities interact with natural fish populations. GoPro cameras were used to collect an underwater video data set on and around shellfish aquaculture farms in an estuary in the NE Pacific from June to August 2017 and June to August 2018 to better understand habitat use by the local fish and crab communities. Images extracted from these videos were labeled to produce a data set that is suitable for use in training computer vision models. The labeled data set contains 77,739 images sampled from the collected video; 67,990 objects (fishes and crustaceans) have been annotated in 30,384 images (the remainder have been annotated as "empty"). The metadata of the data set also indicates whether a physical magenta filter was used during video collection to counteract reduced visibility. These data have the potential to help researchers address system-level and in-depth regional shellfish aquaculture questions related to ecosystem services and shellfish aquaculture interactions.


[Chronic maternal diseases and pregnancy losses. French guidelines].
To review the available data on maternal chronic diseases and pregnancy losses. We searched PubMed and the Cochrane library with pregnancy loss, stillbirth, intrauterine fetal demise, intrauterine fetal death, miscarriage and each maternal diseases of this paper. Antiphospholipid antibodies (anticardiolipin, anti-beta-2-glycoprotein, lupus anticoagulant) should be measured in case of miscarriage after 10WG confirmed by ultrasound (grade B) and an antiphospholipid syndrome should be treated by a combination of aspirin and low-molecular-weight heparin during a subsequent pregnancy (grade A). We do not recommend testing for genetic thrombophilia in case of first trimester miscarriage (grade B) or stillbirth (grade C). Glycemic control should be a goal before pregnancy for women with pregestational diabetes to limit the risks of pregnancy loss (grade A) with a goal of prepregnancy HbA1c<7%. Overt and subclinical hypothyroidisms should be treated by L-thyroxin during pregnancy to reduce the risks of pregnancy loss (grade A). Women who are positive for TPOAb should have TSH concentrations follow-up during pregnancy and subsequently treated by L-thyroxin if they develop subclinical hypothyroidism (grade B). Prepregnancy management of most chronic maternal diseases, ideally through prepregnancy multidisciplinary counseling, reduces the risks of pregnancy loss.


[Evaluation of micronuclei in primary hepatocyte culture in rats treated with organophosphoric compounds].
We have evaluated the genotoxic effect of the three organophosphorous (OPs) insecticides dimethoate (DIM), azinphosmethyl (AZN) and diazinon (DIA) or in combination, at a ratio frequently found in foodstuffs by residual analysis. We have carried out the micronucleus (MN) test on cultured rat hepatocytes which were induced to proliferate by epidermal growth factor (EGF), and treated with the insecticides for 48 hours. The doses tested were chosen on the basis of cytotoxicity tests such as Trypan Blue exclusion and mitotic index inhibition. The results showed that AZN was the most toxic and DIM the least toxic compound. None of the compounds tested showed a genotoxic effect when examined separately. Conversely, a significant increase in MN frequency was observed when the three OPs were used in combination at the lowest concentration used when each compound was tested alone.


Experimental investigation of the role of the splenic vein in gastric venous obstruction after pylorus-preserving pancreatoduodenectomy in the dog.
This study showed that the splenic vein (SV) plays a major role in maintaining gastric blood flow after ligature of peripyloric vessels in the dog. Therefore, SV preservation or alternative venous drainage may be recommended to maintain sufficient gastric blood flow in pylorus-preserving pancreatoduodenectomy (PPPD). In PPPD, we often encounter the problem of gastric venous drainage obstruction, if the splenic-portal vein confluence needs to be resected. This study investigated significance of venous drainage via the left gastric and splenic veins in gastric tissue blood flow. In seven mongrel dogs, gastric tissue blood flow was measured by both laser Doppler flowmetry (LDF) in the antrum and hydrogen gas clearance (HGC) in the antrum and body. Blood flow was measured after the following treatments: 1. No treatment; 2. Duodenal transection; 3. Ligature of the right gastric and gastroepiploic arteries and veins; 4. Transient obstruction of the left gastric vein (LGV); 5. Transient obstruction of the SV with the LGV open; and 6. Obstruction of both the LGV and the SV. As judged by LDF, treatments 2, 3, and 4 did not decrease blood flow, but treatments 5 and 6 significantly decreased it compared with both treatments 1 and 3. By HGC, changes in the antrum and the body were parallel. Duodenal transection did not, but treatments 3 and 4 did decrease blood flow compared with no treatment. Obstruction of the left gastric vein did not, but treatments 5 and 6 did significantly decrease it compared with treatment 3.


Pharmacokinetics of hydralazine, an antihypertensive and DNA-demethylating agent, using controlled-release formulations designed for use in dosing schedules based on the acetylator phenotype.
The antihypertensive hydralazine has recently been repositioned as DNA demethylating for the epigenetic therapy of cancer. As the acetylator phenotype is the key determinant of its plasma levels, the dose of hydralazine needs to be adjusted for the acetylation status of patients. The pharmacokinetics of orally administered hydralazine was evaluated in 26 healthy volunteers (13 slow and 13 fast acetylators) after a single dose of 182 mg administered as a controlled-release tablet. Plasma levels of hydralazine were analyzed in 85 cancer patients treated with this formulation at a dose of 83 mg/day and 182 mg/day for slow and fast acetylators, respectively. The C(max) and t(max) of hydralazine for fast acetylators were 208.4 ± 56.9 SD ng/ml and 2.8 ± 2.5 h, respectively. The corresponding results for slow acetylators were 470.4 ± 162.8 ng/ml, and 4.4 ± 3.1 h. Healthy volunteers who were fast acetylators had no clinically significant changes in blood pressure and heart rate or any other side-effect, however, slow acetylators had transient episodes of headache, tachycardia and faintness. Among 85 cancer patients that received either 182 mg or 83 mg of hydralazine daily, according to their acetylator status, the mean concentrations of hydralazine in plasma were 239.1 ng/ml and 259.2 ng/ml for fast and slow acetylators, respectively. These differences were not significantly different, p = 0.3868. The administration of dose-adjusted controlled-release hydralazine according to the acetylation status of cancer patients yields similar levels of hydralazine.


Interaction of rat Sertoli cells with a collagen lattice in vitro.
Sertoli cells from rats aged 15, 20, and 25 d were subcultured onto collagen-coated, plastic dishes. If the collagen was released from the plastic surface by rimming, the floating rafts of collagen showed uniform shrinkage. If the collagen was allowed to remain attached to the plastic, holes appeared in the collagen with cells from rats aged 25 d but not with those of 15 d. Cells from rats aged 20 d caused fewer and smaller holes to appear. The holes were associated with the formation of clumps of spherical cells from which elongated Sertoli cells extended into the surrounding collagen to end near holes. Rhodamine-phalloidin revealed diffusely distributed actin in the spherical cells in contrast to well-developed microfilaments in the peripheral elongated cells. Addition of cytochalasin B (5 micrograms/ml) to the medium prevented contraction of the floating rafts and the development of holes in the attached collagen. In addition, cytochalasin B caused the peripheral cells to become spherical and to separate from the clumps. Moreover, rhodamine-phalloidin revealed that actin in the peripheral cells occurred as clumps without microfilaments when cytochalasin B was present. When Sertoli cells were subcultured onto silicone rubber films, the cells produced wrinkling of the rubber surface within 4 h of plating. These observations were interpreted to mean that Sertoli cells exert local tractional forces on various substrata. These forces require actin, presumably acting by a contractile mechanism. When the collagen is attached to plastic and the cells are organized into clumps with radiating elongated cells (cells from rats aged 25 d), the tractional forces in the elongated cells reorganize the collagen fibers to produce holes. When cells are uniformly distributed (cells from rats aged 15 d), holes are not formed. When the collagen is released from the plastic surface, tractional forces cause the floating rafts to shrink. These interactions of the cells with collagen are likely to be important in determining the shape of the Sertoli cell in vivo, the polarity of the cell, and its biochemical differentiation.


Cost-Effectiveness of Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy in Treating Brain Metastases.
Single-fraction stereotactic radiosurgery (SRS) is a highly used tool in managing brain metastases, alongside its multifraction counterpart - stereotactic body radiation therapy (SBRT). These radiation therapy techniques have been associated with excellent clinical outcomes, such as decreased local recurrence, increased survival, and improved palliative effects. However, present literature concerning the cost-effectiveness of these techniques remain scarce. Based on the current procedure terminology codes involving services provided during radiation consultation, treatment, and follow-up in our institution, 3-fraction SBRT with a 3-dimensional plan and intensity modulated radiation therapy cost 27% and 17% more than SRS, respectively. A 32% and 34% price increase can, respectively, be seen in 5-fraction SBRT with 3-dimensional plan and intensity modulated radiation therapy delivery sessions relative to 3-fraction SBRT administration. Cost savings between these procedures were associated with the radiation therapy delivery sessions instead of the treatment planning process. These analyses indicate that SRS appears to be a less expensive and time-intensive option than SBRT in our institution. However, additional comparative analyses regarding SRS and SBRT are needed to explore the clinical and financial benefits of these radiation therapy techniques.


The impact of renal insufficiency on clinical outcomes in patients undergoing percutaneous coronary interventions.
We sought to determine the effect of varying degrees of renal insufficiency on death and cardiac events during and after a percutaneous coronary intervention (PCI). Patients with end-stage renal disease have a high mortality from coronary artery disease. Little is known about the impact of mild and moderate renal insufficiency on clinical outcomes after PCI. Cardiac mortality and all-cause mortality were determined for 5,327 patients undergoing PCI from January 1, 1994, to August 31, 1999, at the Mayo Clinic, based on the estimated creatinine clearance or whether the patient was on dialysis. In-hospital mortality was significantly associated with renal insufficiency (p = 0.001). Even after successful PCI, one-year mortality was 1.5% when the creatinine clearance was > or =70 ml/min (n = 2,558), 3.6% when it was 50 to 69 ml/min (n = 1,458), 7.8% when it was 30 to 49 ml/min (n = 828) and 18.3% when it was < 30 ml/min (n = 141). The 18.3% mortality rate for the group with < 30 ml/min creatinine clearance was similar to the 19.9% mortality rate in patients on dialysis (n = 46). The mortality risk was largely independent of all other factors. Renal insufficiency is a strong predictor of death and subsequent cardiac events in a dose-dependent fashion during and after PCI. Patients with renal insufficiency have more baseline cardiovascular risk factors, but renal insufficiency is associated with an increased risk of death and other adverse cardiovascular events, independent of all other measured variables.


Expression of measles virus RNA in peripheral blood mononuclear cells of patients with measles, SSPE, and autoimmune diseases.
In order to characterize measles virus (MV) infection in peripheral blood mononuclear cells (PBMCs), RNA was isolated from PBMCs after PHA-stimulation for 72 hr of 9 patients with acute measles, 16 patients with subacute sclerosing panencephalitis (SSPE), 13 patients with various autoimmune diseases, and 16 healthy control donors. The RNA obtained was screened for the presence of MV N (nucleocapsid) gene specific transcripts of either positive or negative orientation in a S1 nuclease protection assay. The sensitivity of this assay allowed us to detect one infected cell in 20,000 PBMCs or 0.1 to 0.05 copies of MV-specific RNA per cell. Using single-stranded DNA or RNA probes expression of MV genomic RNA of negative polarity could be detected in only one case of acute measles and one healthy control donor. Conversely, N-specific transcripts of positive polarity, indicating active transcription, could only be detected in patients with acute measles. In addition, in infected PBMCs and in a persistently MV-infected B cell line positive stranded N-specific transcripts containing leader usually present at very low frequency have been found in relatively increased amounts in comparison with transcripts lacking leader. Whereas the ratio of these RNA species during lytic infection with MV in Vero cells is about 1:50, the ratio found here ranges from 1:3 to 1:10. This altered ratio indicates a specific regulation of MV specific transcription in cells of lymphoid origin that has not been found in any other cell system analyzed.


Effect of maternal curcumin supplementation on intestinal damage and the gut microbiota in male mice offspring with intra-uterine growth retardation.
The present study investigated whether maternal curcumin supplementation might protect against intra-uterine growth retardation (IUGR) induced intestinal damage and modulate gut microbiota in male mice offspring. In total, 36 C57BL/6 mice (24 females and 12 males, 6-8 weeks old) were randomly divided into three groups based on the diet before and throughout pregnancy and lactation: (1) normal protein (19%), (2) low protein (8%), and (3) low protein (8%) + 600 mg kg-1 curcumin. Offspring were administered a control diet until postnatal day 35. Maternal curcumin supplementation could normalize the maternal protein deficiency-induced decrease in jejunal SOD activity (NP = 200.40 ± 10.58 U/mg protein; LP = 153.30 ± 5.51 U/mg protein; LPC = 185.40 ± 9.52 U/mg protein; P < 0.05) and T-AOC content (NP = 138.90 ± 17.51 U/mg protein; LP = 84.53 ± 5.42 U/mg protein; LPC = 99.73 ± 12.88 U/mg protein; P < 0.05) in the mice offspring. Maternal curcumin supplementation increased the maternal low protein diet-induced decline in the ratio of villus height-to-crypt depth (NP = 2.23 ± 0.19; LP = 1.90 ± 0.06; LPC = 2.56 ± 0.20; P < 0.05), the number of goblet cells (NP = 12.72 ± 1.16; LP = 7.04 ± 0.53; LPC = 13.10 ± 1.17; P < 0.05), and the ratio of PCNA-positive cells (NP = 13.59 ± 1.13%; LP = 2.42 ± 0.74%; LPC = 6.90 ± 0.96%; P < 0.05). It also reversed the maternal protein deficiency-induced increase of the body weight (NP = 13.00 ± 0.48 g; LP = 16.49 ± 0.75 g; LPC = 10.65 ± 1.12 g; P < 0.05), the serum glucose levels (NP = 5.32 ± 0.28 mmol/L; LP = 6.82 ± 0.33 mmol/L; LPC = 4.69 ± 0.35 mmol/L; P < 0.05), and the jejunal apoptotic index (NP = 6.50 ± 1.58%; LP = 10.65 ± 0.75%; LPC = 5.24 ± 0.71%; P < 0.05). Additionally, maternal curcumin supplementation enhanced the gene expression level of Nrf2 (NP = 1.00 ± 0.12; LP = 0.73 ± 0.10; LPC = 1.34 ± 0.12; P < 0.05), Sod2 (NP = 1.00 ± 0.04; LP = 0.85 ± 0.04; LPC = 1.04 ± 0.04; P < 0.05) and Ocln (NP = 1.00 ± 0.09; LP = 0.94 ± 0.10; LPC = 1.47 ± 0.09; P < 0.05) in the jejunum. Furthermore, maternal curcumin supplementation normalized the relative abundance of Lactobacillus (NP = 31.56 ± 6.19%; LP = 7.60 ± 2.33%; LPC = 17.79 ± 2.41%; P < 0.05) and Desulfovibrio (NP = 3.63 ± 0.93%; LP = 20.73 ± 3.96%; LPC = 13.96 ± 4.23%; P < 0.05), and the ratio of Firmicutes/Bacteroidota (NP = 2.84 ± 0.64; LP = 1.21 ± 0.30; LPC = 1.79 ± 0.15; P < 0.05). Moreover, Lactobacillus was positively correlated with the SOD activity, and it was negatively correlated with Il - 1β expression (P < 0.05). Desulfovibrio was negatively correlated with the SOD activity and the jejunal expression of Sod1, Bcl - 2, Card11, and Zo - 1 (P < 0.05). Maternal curcumin supplementation could improve intestinal integrity, oxidative status, and gut microbiota in male mice offspring with IUGR.


Feasibility of Find cases Actively, Separate safely and Treat effectively (FAST) strategy for early diagnosis of TB in Nepal: An implementation research.
Tuberculosis is one of the leading causes of death worldwide. Diagnosing TB in an early stage and initiating effective treatment is one of the best ways to reduce the burden of tuberculosis. Feasibility of Find cases Actively, Separate safely and Treat effectively (FAST) Strategy helps to improve the early diagnosis of tuberculosis cases among inpatient settings as well as out patient department patients and prevent TB transmission in hospital. This study aimed to assess the feasibility of the FAST strategy, organizational factors, technical factors, barriers and enablers for the proper implementation of the FAST strategy in Nepal. A qualitative study was conducted from April 2019 to August 2019. Data was collected by using focus group discussion, key informant interviews, and client exit interviews. A retrospective research was conducted in different hospitals in Nepal where FAST strategy was implemented. The patients, health care workers, province, district, and National level stakeholders were interviewed. Thematic analysis was used to assess the feasibility as well as barriers and enablers of the FAST strategy. Study identified that the 'current setting' of implementation and service delivery arrangement at hospitals were not well arranged as per requirements. The research findings showed hospital ownership is crucial for mobilizing staff and proper space management inside hospitals. Study identified that unavailability of a separate room, limited capacity of GeneXpert machine, irregular supply of GeneXpert cartridge, and insufficient human resources for screening and counseling are the major barriers of FAST implementation in Nepal. FAST strategy is feasible to implement in healthcare settings in Nepal although the technical and organizational factors should be managed to ensure effective function of the strategy as per the approach. Hospital ownership is essential to mobilize health workers, improve client flow system and proper space management for FAST services.


Superoxide dismutase down-regulation and the oxidative stress is required to initiate pupation in Bombyx mori.
Perhaps, oxidative stress progresses pupation in some Lepidopteran insects; however, the reasons for this remain obscure. In our previous study, we clarified Bombyx mori SOD1 (BmSOD1) and B. mori SOD2 (BmSOD2) proteins respond in common to ultraviolet irradiation (UV) oxidative stress and metamorphosis. This result strongly suggested pupation initiates by oxidative stress and might mediate by down-regulation of expression of BmSOD1 and BmSOD2 proteins. Thus, we examined about these relationships in B. mori in this study. In the microarray data reanalysis, we found the Notch signaling pathways as the common pathways in pupation and UV oxidative stress in B. mori. Also, we showed a molting hormone, 20-hydroxyecdysone, leads not only generation of superoxide but also downregulation of the expression of BmSOD proteins during pupation in B. mori. Our findings can contribute to a deeper understanding of how biological defense systems work against environmental oxidative stress.


Differences in the distributional pattern of CRF-, oxytocin-, and vasopressin-immunoreactive nerve fibers in the median eminence of the rat.
Conspicuous differences in the distributional pattern of nerve fibers containing corticotropin-releasing factor (CRF) or posterior lobe hormones, respectively, were shown in the median eminence of the adult male rat by means of immunoperoxidase histochemistry, with the use of anti-CRF, anti-oxytocin, and anti-vasopressin sera. In the rostral and central divisions of the median eminence, a high concentration of CRF-immunoreactive nerve fibers was found in the median portion of the external layer; these fibers terminated on the capillary loops of the hypophysial portal system. In the caudal division of the median eminence, the CRF-immunoreactive nerve fibers were located in the median to paramedian portions of the external layer. Numerous oxytocin- and vasopressin-immunoreactive nerve fibers were observed evenly distributed throughout the internal layer of the median eminence. In the external layer, a small number of the oxytocin- and vasopressin-containing nerve fibers was found around the capillary loops, particularly in the median to paramedian portions. The distributional patterns of the CRF and the posterior lobe hormones in the hypothalamo-hypophysial system and their functional interrelationship are discussed.


Effect of temperature on development and reproduction of Neoseiulus barkeri (Acari: Phytoseiidae) fed on Aleuroglyphus ovatus.
The effect of five constant temperatures (16, 20, 24, 28 and 32°C) on the development, survival and reproduction of Neoseiulus barkeri Hughes fed on Aleuroglyphus ovatus Toupeau (Acari: Acaridae) was examined in the laboratory at 85% relative humidity. Development time of different immature stages decreased with increasing temperature, total egg-to-adult development time varied from 5.0 ± 0.13 to 17.5 ± 0.29 days. The lower thermal threshold for development was 9.7 ± 2.48°C and the thermal constant from egg to adult was 111.1 ± 12.34 degree-days. Pre- and post-oviposition period and female longevity all shortened as temperature increased. The longest oviposition period was observed at 24°C with 20.4 ± 1.13 days. At 20, 24, 28 and 32°C, mated females laid on average 0.7 ± 0.08, 1.5 ± 0.04, 1.6 ± 0.11 and 1.5 ± 0.11 eggs per day, respectively, but no eggs were laid at 16°C. Both the maximum fecundity (30.9 eggs per female) and the highest intrinsic rate of increase (r (m) = 0.166) were obtained at 28°C. The results of this study indicated that a mass rearing of N. barkeri with A. ovatus as prey is feasible at the appropriate temperature.


Caution Is Needed When Using Niche Models to Infer Changes in Species Abundance: The Case of Two Sympatric Raptor Populations.
Despite the mounting evidence supporting positive relationships between species abundance and habitat suitability, the capacity of ecological niche models (ENMs) to capture variations in population abundance remains largely unexplored. This study focuses on sympatric populations of hen harrier (Circus cyaneus) and Montagu's harrier (Circus pygargus), surveyed in 1997 and 2017 in an upland moor area in northwestern Spain. The ENMs performed very well for both species (with area under the ROC curve and true skill statistic values of up to 0.9 and 0.75). The presence of both species was mainly correlated with heathlands, although the normalized difference water index derived from Landsat images was the most important for hen harrier, indicating a greater preference of this species for wet heaths and peat bogs. The findings showed that ENM-derived habitat suitability was significantly correlated with the species abundance, thus reinforcing the use of ENMs as a proxy for species abundance. However, the temporal variation in species abundance was not significantly explained by changes in habitat suitability predicted by the ENMs, indicating the need for caution when using these types of models to infer changes in population abundance.


How Are Information and Communication Technologies Supporting Routine Outcome Monitoring and Measurement-Based Care in Psychotherapy? A Systematic Review.
Psychotherapy has proven to be effective for a wide range of mental health problems. However, not all patients respond to the treatment as expected (not-on-track patients). Routine outcome monitoring (ROM) and measurement-based care (MBC), which consist of monitoring patients between appointments and using this data to guide the intervention, have been shown to be particularly useful for these not-on-track patients. Traditionally, though, ROM and MBC have been challenging, due to the difficulties associated with repeated monitoring of patients and providing real-time feedback to therapists. The use of information and communication technologies (ICTs) might help reduce these challenges. Therefore, we systematically reviewed evidence regarding the use of ICTs for ROM and MBC in face-to-face psychological interventions for mental health problems. The search included published and unpublished studies indexed in the electronic databases PubMed, PsycINFO, and SCOPUS. Main search terms were variations of the terms "psychological treatment", "progress monitoring or measurement-based care", and "technology". Eighteen studies met eligibility criteria. In these, ICTs were frequently handheld technologies, such as smartphone apps, tablets, or laptops, which were involved in the whole process (assessment and feedback). Overall, the use of technology for ROM and MBC during psychological interventions was feasible and acceptable. In addition, the use of ICTs was found to be effective, particularly for not-on-track patients, which is consistent with similar non-ICT research. Given the heterogeneity of reviewed studies, more research and replication is needed to obtain robust findings with different technological solutions and to facilitate the generalization of findings to different mental health populations.


Mitral valve dysplasia in eight English Springer Spaniels.
To describe the signalment, physical examination, and echocardiographic findings of a series of English Springer Spaniels (ESSs) diagnosed with congenital mitral valve dysplasia (MD). Eight client-owned ESSs with congenital MD referred for murmur investigation and/or suspected congestive heart failure (CHF). Retrospective case series. Medical records and echocardiograms were reviewed to collect relevant data. Echocardiograms were assessed for the following abnormalities consistent with MD: thickened valve leaflets or leaflet tips, a 'hockey stick' appearance to the valve leaflets, abnormal length of one leaflet with respect to the other, and tethering of one or both leaflets to the papillary muscles. All eight dogs showed the typical echocardiographic lesions associated with MD: thickened leaflet tips (5/8), 'hockey stick' appearance (5/8), elongated anterior leaflet (4/8), tethering of one or both leaflets (7/8). Seven of the eight dogs presented in CHF. Six of the eight dogs had left ventricular dilation in both systole and diastole. Two of the eight dogs had reduced systolic function as assessed by ejection fraction/fractional shortening; however end-systolic volume index was increased in 6/8 dogs. Two dogs subsequently developed atrial fibrillation. Congenital MD should be considered in ESSs with a left-sided apical systolic murmur, particularly in younger dogs. The valve changes seen are similar to those reported in other breeds with MD (thickened leaflet tips, hockey stick appearance to open leaflet tips, abnormal leaflet tethering, abnormally shaped leaflets) and may result in marked remodeling and CHF.


Locked nucleic acids and intercalating nucleic acids in the design of easily denaturing nucleic acids: thermal stability studies.
Intercalating nucleic acids (INA(R)s) with insertions of (R)-1-O-(1-pyrenylmethyl)glycerol were hybridized with locked nucleic acids (LNAs). INA/LNA duplexes were found to be less stable than the corresponding DNA/LNA duplexes when the INA monomer was inserted as a bulge close to the LNA monomers in the opposite strand. This property was used to make "quenched" complements that possess LNA in hairpins and in duplexes and are consequently more accessible for targeting native DNA. The duplex between a fully modified 13-mer LNA sequence and a complementary INA with six pyrene residues inserted after every second base as a bulge was found to be very unstable (Tm=30.1 degrees C) in comparison with the unmodified double-stranded DNA (Tm=48.7 degrees C) and the corresponding duplexes of LNA/DNA (Tm=81.6 degrees C) and INA/DNA (Tm=66.4 degrees C). A thermal melting experiment of a mixture of an LNA hairpin, with five LNA nucleotides in the stem, and its complementary DNA sequence gave a transition with an extremely low increase in optical density (hyperchromicity). When two INA monomers were inserted into the stem of the LNA hairpin, the same experiment resulted in a significant hyperchromicity comparable with the one obtained for the corresponding DNA/DNA duplex.


Temporal variations in early gut microbial colonization are associated with allergen-specific immunoglobulin E but not atopic eczema at 2 years of age.
Intestinal microbiota undergoes substantial development during the first 2 years of life, important for intestinal immunologic development and maturation influencing systemic immune responses. We aimed to investigate, using a prospective study design, whether allergen-specific IgE (sIgE) and atopic eczema are associated with variations in gut microbial colonization patterns in an unselected population during the first 2 years of life. Faeces from 94 infants were repeatedly sampled from 10 days, 4 months, 1 and 2 years postnatal and analysed for 12 different bacterial species by quantitative real-time PCR. Venous blood samples from the infants were collected at 2 years of age and were analysed for sIgE for 12 specific allergens. The temporal gut colonization patterns for 42 sIgE-positive (sIgE≥0.35 kU/L) and 52 sIgE-negative children (sIgE<0.1 kU/L) were then compared. The association between colonization pattern and phenotype as atopic eczema according to UK Working Party (UKWP) criteria were also described. Subjects with atopic sensitization had lower levels of Escherichia coli at 4 months and 1 year, higher levels of Bifidobacterium longum at 1 year and lower levels of Bacteroides fragilis at 2 years. For E. coli and B. longum, the differences were only transient and had disappeared by 2 years of age. For other species, there were no differences in colonization patterns, and we found no association between colonization pattern and atopic eczema. We found temporal and transient variations in gut microbial colonization patterns associated with differences in sIgE sensitization at 2 years of age. A full understanding of the principles and mechanisms that underlie intestinal microbial colonization and diversity and host-microbiota relationships will be pivotal for the development of therapeutic approaches that manipulate the intestinal microbiota to maintain human health. [ ISRCTN28090297].


Love in the Time of COVID-19: The Social Dimensions of Intimate Life under Lockdown.
Although popular media across the United States reported that the coronavirus disease 2019 COVID pandemic incited dramatic transformations in personal relationships, identities, and practices, little sociological research examines these developments. What exists elaborates the "how" and "how much" of sex, the frequency of sexual conduct, and changes in the patterning of sexual behavior. In this study of the intimate trajectories of 46 young adults, conducted during the height of U.S. quarantine restrictions in 2020 and early 2021, the authors explore the "whys" of sex. They find that the exogenous force of the pandemic profoundly altered individual relationship trajectories, prompted sexual introspection projects, shifted understandings of sexual risk, and promoted new modes of intimacy. These findings suggest that pandemic life reached deep into subjective self-understandings and ways of relating to others. They also reveal the benefits of foregrounding cultural meanings over behaviors, changes in thoughts over actions, and social processes over individual outcomes.


Coronary artery changes in congenital coronary-cameral fistulas evaluated by computed tomographic angiography.
The study sought to determine coronary artery diameter in congenital coronary-cameral fistula (cCCF), factors associated with coronary artery aneurysm, coronary artery changes after fistula closure, and computed tomographic (CT) findings after treatment. We retrospectively reviewed CT findings of the cCCF for origins, terminations, fistula length, complexities, and Sakakibara classification. Coronary artery diameter was expressed as coronary artery Z score. Fistula features associated with coronary artery aneurysm were analyzed. Post-fistula closures were analyzed for coronary artery dilatation, coronary thrombosis, complete fistula closure, and fistula thrombosis. Twenty-five patients (median age 33 months, interquartile range, IQR 25-48) were included. Coronary feeders and terminations were frequently right coronary artery (48%) and right ventricle (56%), respectively. Fistula aneurysm occurred in 52% of cases. Mean coronary artery Z score was 13.03 ± 6.36 with a high incidence of giant coronary artery aneurysm (68%). We found no statistically significant risk factors associated with coronary artery aneurysm (p value range 0.075-0.370). Median duration of the follow-up CT after closure of the fistulas was 6.4 months (IQR 5.0-8.7). Coronary artery Z score significantly decreased by 0.82 (IQR 0.28-1.35), p = 0.006 and coronary thrombosis occurred in 23% of cases during follow-up. Large coronary aneurysm is common in cCCF. No characteristic feature of the fistula influencing coronary artery aneurysm is identified. There is a diminution in coronary artery Z score after fistula closure. Coronary thrombosis is a major complication after treatment.


Colonic perforation due to inadvertent intraperitoneal LVAD driveline placement.
Left ventricular assist devices (LVAD) are placed for patients with advanced heart failure or cardiogenic shock as destination therapy or as a bridge to cardiac transplantation. Significant complications associated with LVAD placement include bleeding, infection, pump thrombosis, right heart failure, device malfunction and stroke. The case below illustrates inadvertent intraperitoneal driveline placement causing colonic perforation and the subsequent management. A 54 year old male with a history of Wolff-Parkinson-White syndrome resulting in multiple readmissions for heart failure, ultimately required placement of a left ventricular assist device (LVAD). Several weeks later, he was found to have stool draining from the driveline site. The patient was taken to the operating room for limited exploration by the Cardiothoracic Surgery team and a bowel injury was identified and repaired. Three days after this repair, stool was once again leaking from the driveline site, requiring re-exploration by the Acute Care Surgery team. Intraoperatively, the prior repair was found to be leaking and multiple intra-abdominal abscesses were discovered. The transverse colon was resected and left in discontinuity. On a planned second look operation, the LVAD driveline was relocated to be extra-peritoneal and a colostomy was formed. This case demonstrates the importance of early recognition and involvement of an Acute Care Surgeon in the management of this complex problem. Appropriate treatment involves a complete exploration, source control, driveline relocation and possible fecal diversion. Although the incidence of this complication is low, it must be considered in the differential in a septic LVAD patient.