Flow-induced prostaglandin E2 release regulates Na and K transport in the collecting duct.
Fluid shear stress (FSS) is a critical regulator of cation transport in the collecting duct (CD). High-dietary sodium (Na) consumption increases urine flow, Na excretion, and prostaglandin E(2) (PGE(2)) excretion. We hypothesize that increases in FSS elicited by increasing tubular flow rate induce the release of PGE(2) from renal epithelial cells into the extracellular compartment and regulate ion transport. Media retrieved from CD cells exposed to physiologic levels of FSS reveal several fold higher concentration of PGE(2) compared with static controls. Treatment of CD cells with either cyclooxygenase-1 (COX-1) or COX-2 inhibitors during exposure to FSS limited the increase in PGE(2) concentration to an equal extent, suggesting COX-1 and COX-2 contribute equally to FSS-induced PGE(2) release. Cytosolic phospholipase A2 (cPLA2), the principal enzyme that generates the COX substrate arachidonic acid, is regulated by mitogen-activated protein-kinase-dependent phosphorylation and intracellular Ca(2+) concentration ([Ca(2+)](i)), both signaling processes, of which, are activated by FSS. Inhibition of the ERK and p38 pathways reduced PGE(2) release by 53.3 ± 8.4 and 32.6 ± 11.3%, respectively, while antagonizing the JNK pathway had no effect. In addition, chelation of [Ca(2+)](i) limited the FSS-mediated increase in PGE(2) concentration by 47.5 ± 7.5% of that observed in untreated sheared cells. Sheared cells expressed greater phospho-cPLA2 protein abundance than static cells; however, COX-2 protein expression was unaffected (P = 0.064) by FSS. In microperfused CDs, COX inhibition enhanced flow-stimulated Na reabsorption and abolished flow-stimulated potassium (K) secretion, but did not affect ion transport at a slow flow rate, implicating that high tubular flow activates autocrine/paracrine PGE(2) release and, in turn, regulates flow-stimulated cation transport. In conclusion, FSS activates cPLA2 to generate PGE(2) that regulates flow-mediated Na and K transport in the native CD. We speculate that dietary sodium intake modulates tubular flow rate to regulate paracrine PGE(2) release and cation transport in the CD.


Temporal changes in treatment patterns by age group and functional status before and after PD-1/L1 inhibitor approvals in advanced urothelial carcinoma.
Metastatic urothelial carcinoma (mUC) has poor prognosis. A high unmet need exists for novel treatment for those who are unfit for platinum-based chemotherapy. We aimed to describe real-world temporal changes in patient characteristics and 1L treatment selection for mUC patients in the United States following the approval of anti-PD-1/L1 treatments. This study was a retrospective, observational study using anonymized and structured oncology electronic medical record (EMR) data from IQVIA and the US Oncology Network iKnowMed (USON). After approval of 1L anti-PD-1/L1 treatment for mUC, there is a marked increase in the use of 1L anti-PD-1/L1 monotherapies, accompanied by a proportional decrease in 1L platinum-based treatments and non-guideline-based therapy; particularly among the elderly (> 75 years) and those with poor ECOG performance status (ECOG PS 2+). Anti-PD-1/L1 monotherapies fulfill the prior unmet need of frail mUC patients who are ineligible for platinum-based therapies.


L-Lactate transport into rat heart mitochondria and reconstruction of the L-lactate/pyruvate shuttle.
In vitro reconstruction of the L-lactate/pyruvate shuttle has been performed, which allows NADH oxidation outside rat heart mitochondria. Such a shuttle occurs due to the combined action of the novel mitochondrial L-lactate/pyruvate antiporter, which differs from the monocarboxylate carrier, and the mitochondrial L-lactate dehydrogenase. The rate of L-lactate/pyruvate antiport proved to regulate the shuttle in vitro.


Campylobacter pylori infection and its relation to chronic gastritis. An endoscopic, bacteriologic, and histomorphologic study.
Campylobacter pylori was isolated from 27 of 61 gastric antral biopsy specimens and from 8 of 61 duodenal biopsy specimens. A significant correlation between the occurrence of C. pylori and chronic active gastritis was demonstrated. However, the presence of the bacterium on normal mucosa weakens the theory of C. pylori as a primary causal organism. There was a significant correlation between isolation of C. pylori and erosive lesions in the antral mucosa as diagnosed by endoscopy. No correlation was found between endoscopic findings and histologically verified chronic active gastritis. The microbiologic examinations in this study showed a high degree of homogeneity between the isolated strains of C. pylori. A 3-OH-octadecanoic acid of the bacterial cell wall seemed to be specific for this organism and was identified in all our isolates and in the type strain of C. pylori. We therefore conclude that all Campylobacter-like organisms isolated in this study belonged to one taxonomic unit.


Preparation of Nano-TiO2 by a Surfactant-Free Microemulsion-Hydrothermal Method and Its Photocatalytic Activity.
The TiO2 nanoparticles with high photocatalytic activity were prepared by the surfactant-free microemulsion (SFME)-hydrothermal method at lower temperatures using oil-in-water SFME systems as templates. The phase diagram of the SFME ethyl acetate (EA)/propan-2-ol/water was determined by electrical conductivity and UV-visible spectroscopy. The synthesized TiO2 nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, and N2 adsorption-desorption techniques. They were all assigned to the anatase phase and showed type IV adsorption-desorption isotherms with type H2 hysteresis loops. As the EA content (fO) of the SFME decreases, the Brunauer-Emmett-Teller (BET) specific surface area (SBET) of the TiO2 nanoparticles increases. This results in an increase in the photocatalytic activity of the TiO2 nanoparticles. With an increase in temperature, the photocatalytic activity of the TiO2 nanoparticles increases significantly, whereas the SBET values decrease and the crystal size increases. Under the same conditions, the degradation rate of the TiO2 prepared at 190 °C reaches 97%, which is significantly higher than that of Degussa P-25 (66%). This may be due to the use of the SFME system to synthesize the TiO2 nanoparticles, which avoids the blocking effects of surfactant molecules on the active sites of the nanoparticles.


Microbial diversity in individuals and their household contacts following typical antibiotic courses.
Antibiotics are a mainstay of treatment for bacterial infections worldwide, yet the effects of typical antibiotic prescriptions on human indigenous microbiota have not been thoroughly evaluated. We examined the effects of the two most commonly prescribed antibiotics (amoxicillin and azithromycin) in the USA to discern whether short-term antibiotic courses may have prolonged effects on human microbiota. We sampled the feces, saliva, and skin specimens from a cohort of unrelated, cohabitating individuals over 6 months. An individual in each household was given an antibiotic, and the other a placebo to discern antibiotic impacts on microbiota, as well as determine whether antibiotic use might reshape the microbiota of each household. We observed household-specific patterns of microbiota on each body surface, which persevered despite antibiotic perturbations. While the gut microbiota within an individual became more dissimilar over time, there was no evidence that the use of antibiotics accelerated this process when compared to household members. There was a significant change in microbiota diversity in the gut and mouth in response to antibiotics, but analogous patterns were not observed on the skin. Those who received 7 days of amoxicillin generally had greater reductions in diversity compared to those who received 3 days, in contrast to those who received azithromycin. As few as 3 days of treatment with the most commonly prescribed antibiotics can result in sustained reductions in microbiota diversity, which could have implications for the maintenance of human health and resilience to disease.


[Recording intracellular potentials of viscero-nociceptive neurons in posterior group of thalamic nuclei (PO) and their labeling with HRP intracellularly in cats].
Intracellular potentials (ICP) of the neurons in PO evoked by stimulating greater splanchnic nerve (GSN) were recorded in 42 cats. The resting potentials and action potentials induced by stimulating GSN were 53.74 +/- 11.68 mV and 29.44 +/- 9.22 mV respectively. Owing to intensity of the stimulation we can record EPSP and single spike or polyspikes on it. The action potentials derived from stimulating GSN (related action potentials) were inhibited by injection of morphine intravenously. On the basis of recording ICP, we also labeled 2 related neurons with stimulation of GSN and 2 unrelated ones. Differences between two kinds of the neurons were compared preliminarily. The ICP of the related neuron with stimulating GSN were inhibited by stimulating Amygdala too. Factors influencing amplitude of action potential in intracellular recording, criteria of determining nociceptive neuron and inhibition derived from stimulating Amygdala were also discussed.


Effect of bone morphogenetic protein-15 on gonadotropin-stimulated synthesis of hyaluronan and progesterone in porcine ovarian follicle.
Bone morphogenetic protein-15 (BMP-15), an oocyte-derived growth factor, has been shown to play integral roles in regulation of ovarian follicular function in mammals. Despite the recognition of the physiological importance of the BMP system in regulation of gonadotropin action in the ovary, molecular mechanisms of BMP-15 effect on oocyte and somatic follicular cell functions remain poorly understood. The objective of this study was to determine the effect of BMP-15 on the FSH/LH-stimulated synthesis of hyaluronan (HA) by oocyte cumulus complexes (OCC) and progesterone by OCC and granulosa cells (GC) in the presence or absence of serum using primary porcine cultures. In addition, the effect of BMP-15 on oocyte maturation- and steroidogenesis-related transcripts after 4, 8, 16, and 24 hours of cultivation was evaluated using real-time RT-PCR. We demonstrated that the FSH/LH-induced cumulus expansion was accompanied by a significant increase in CD44, PTGS2, CYP11A1 (at 4 h) and AREG, HAS2, TNFAIP6, STAR (at 8 h) mRNAs. While FSH/LH-stimulated total HA synthesis by OCC was not affected by BMP-15 in serum-supplemented medium, its retention within the complex was significantly increased after the action of BMP-15 in comparison to FSH/LH alone (P < 0.001; 65% versus 35%, respectively). Moreover, we detected a significant increase in the expression of AREG and TNFAIP6 (both at 16 h), and CYP11A1 (at 24 h) in FSH/LH-stimulated OCC due to the action of BMP-15 compared to complexes cultured only with FSH/LH. In the presence of serum, BMP-15 markedly increased FSH/LH-stimulated progesterone secretion by OCC (about 69%) and induced a significant decrease in FSH/LH-induced progesterone release by GC (about 35%) compared to FSH/LH alone. The present results indicate that the addition of BMP-15 to the gonadotropin-stimulated OCC cultured in serum-supplemented medium might improve oocyte-cumulus maturation.


Plant genome engineering with sequence-specific nucleases.
Recent advances in genome engineering provide newfound control over a plant's genetic material. It is now possible for most bench scientists to alter DNA in living plant cells in a variety of ways, including introducing specific nucleotide substitutions in a gene that change a protein's amino acid sequence, deleting genes or chromosomal segments, and inserting foreign DNA at precise genomic locations. Such targeted DNA sequence modifications are enabled by sequence-specific nucleases that create double-strand breaks in the genomic loci to be altered. The repair of the breaks, through either homologous recombination or nonhomologous end joining, can be controlled to achieve the desired sequence modification. Genome engineering promises to advance basic plant research by linking DNA sequences to biological function. Further, genome engineering will enable plants' biosynthetic capacity to be harnessed to produce the many agricultural products required by an expanding world population.


Transcriptome Analysis Reveals a Gene Expression Pattern That Contributes to Sugarcane Bud Propagation Induced by Indole-3-Butyric Acid.
Sugarcane is a cash crop that plays an integral part in the sugar industry. The Sustainable Sugarcane Initiative (SSI) has been adopted globally, ensuring enough and aiming for more yield, helping increase disease-free sugarcane cultivation. Single-bud seeds could be the best approach for sugarcane cultivation. Indole-3-butyric acid (IBA) is a rooting agent utilized significantly in seedling propagation. Greenhouse experiment results discovered the significant growth promotion in sugarcane seedlings and accumulation of plant hormones at 100 ppm IBA. Next, we performed transcriptomic analysis of sugarcane buds using RNA sequencing and compared their gene expression during root development due to affect of IBA (100 ppm). A total of 113,475 unigenes were annotated with an average length of 836 bp (N50 = 1,536). The comparative RNA-seq study between the control (CK) and IBA-treated (T) buds showed significant differentially expressed unigenes (494 upregulated and 2086 downregulated). The IBA influenced major biological processes including metabolic process, the cellular process, and single-organism process. For cellular component category, cell, cell part, organelle, membrane, and organelle part were mainly affected. In addition, catalytic activity and binding were primarily affected in the molecular function categories. Furthermore, the expression of genes related to plant hormones and signaling pathways was analyzed by qRT-PCR, which was consistent with the RNA-seq expression profile. This study provides new insights into the IBA response to the bud sprouting in sugarcane based on RNA sequencing, and generated information could help further research on breeding improvement of sugarcane.


The millipede genus Julus Linnaeus, 1758 in the Caucasus (Diplopoda: Julida: Julidae).
The genus Julus includes seven species already described from the Caucasus region: J. alexandrae Evsyukov, 2016; J. colchicus Lohmander, 1936; J. jedryczkowskii Golovatch, 1981; J. kubanus Verhoeff, 1921; J. lignaui Verhoeff, 1910; J. lindholmi Lohmander, 1936; and J. subalpinus Lohmander, 1936, as well as two new species: J. khostensis sp. n., from the Krasnodar Province, and, J. dagestanus sp. n., from the Republic of Dagestan, both in Russia. All nine species are described, illustrated and keyed, their morphological variations outlined, and distributions mapped, based on the literature data and abundant new samples. Altitudinal distribution patterns are also discussed.


One hundred twenty-five adult patients with primary acute leukemia autografted with marrow purged by mafosfamide: a 10-year single institution experience.
A total of 125 acute leukemia adult patients were autografted with bone marrow (BM) purged by mafosfamide (ASTA Z) during the period of January 1983 to January 1993. The median follow-up period was 64 months (range, 3 to 126). There were 84 acute myeloblastic leukemias (AMLs) and 41 acute lymphoblastic leukemias (ALLs). At time of autologous BM transplantation (ABMT); 64 AMLs were in first complete remission (CR1), and 20 were in second CR (CR2); 35 ALL were in CR1, and 6 were in CR2. The median age of the patients was 33 years (range, 16 to 55). The median interval between achieving CR and autografting was 5 months (range, 1.3 to 23). The pretransplant regimen consisted of cyclophosphamide (120 mg/kg) and total body irradiation. All patients were grafted with autologous BM treated in vitro with mafosfamide used at levels individually adjusted in 95 patients and at a standard dose in 30 patients. The initial richness in granulomacrophagic progenitors (CFU-GM) of the harvested BMs was 5.16 x 10(4) CFU-GM/kg (range, 0.55 to 33). After mafosfamide purging, the residual CFU-GM number was 0.021 x 10(4)/kg (range, 0 to 1.78). The probability of successful engraftment was significantly higher and the time to engraftment was significantly shorter in ALL. Of 33 patients grafted with BM containing no residual CFU-GM, those with AML (n = 22) had platelet recoveries that were significantly longer than those for AML patients receiving BM with residual CFU-GM. At 8 years, patients autografted in CR1 for AML and ALL had a leukemia-free survival (LFS) of 58% and 56%, respectively, with a relapse incidence (RI) of 25% and 37%, respectively. Patients autografted in CR2 for AML had an LFS of 34% and an RI of 48% at 5 years. The incidence of late relapses was significantly higher in ALLs. By multivariate analysis, four factors were found to influence favorably engraftment in addition to a diagnosis of ALL, a younger age, ABMT performed in CR1, the adjusted dose technique of purging, and a shorter interval from CR to ABMT. Two factors were correlated with a better outcome. (1) The LFS was significantly higher and the transplant-related mortality significantly lower in patients who received richer BM. (2) The RI was significantly lower in patients autografted within 150 days from CR. Our results reinforce the view that ABMT is one approach to improve the outcome of adult patients with acute leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Three new species of Ligophorus (Monogenea: Dactylogyridae) on the gills of Mugil cephalus (Teleostei: Mugilidae) from the Japan Sea.
Comparative morphology and multivariate morphometric analysis of monogeneans collected on flathead mullets Mugil cephalus from 2 Russian localities of the Japan Sea revealed the presence of 3 new species of Ligophorus, namely, L. domnichi n. sp., L. pacificus n. sp., and L. cheleus n. sp., which are described herein. So far, only 1 species of dactylogyrid monogenean identified as Ligophorus chabaudi was known on flathead mullets in this sea, but after comparison with the present material, we propose that this form actually represents L. domnichi n. sp. Results support previous zoogeographical evidence, suggesting that flathead mullets from different seas harbor different species complexes of Ligophorus. One interesting finding is that the 3 new species have a U-shaped ovary, whereas ovate ovaries have been reported in previous descriptions of species of the genus, e.g., L. vanbenedenii, L. parvicirrus, L. imitans, and L. chongmingensis. The U-shaped ovary was revealed only when the worms were observed in lateral view. The additional examination of L. vanbenedenii, L. parvicirrus, L. imitans, and L. pilengas specimens from our collections also revealed a U-shaped ovary in these forms as well. Further studies should establish whether or not this character is shared by all members of the genus.


Is it better to be moral than smart? The effects of morality and competence norms on the decision to work at group status improvement.
Three studies examined strategies of status improvement in experimentally created (Study 1 and 2) and preexisting (Study 3) low-status groups. Theory and prior research suggested that an in-group norm that established a particular strategy of status improvement as moral (rather than competent) would have a greater effect on individuals' decision to work at this strategy. Both Study 1 and Study 2 found that morality norms had a greater impact than competence norms on individuals' decision to work at group (rather than individual) status improvement. In both studies participants also needed less time to decide on a strategy of status improvement when it is was encouraged by a morality norm rather than a competence norm. Study 3 used a preexisting low-status group (i.e., Southern Italians) to further confirm that morality norms have a greater effect on the decision to work at group status improvement than do competence norms. Results are discussed in terms of social influence and identity management strategies.


Do Early Fetal Measurements and Nuchal Translucency Correlate With Term Birth Weight?
Traditionally, physiological variation in fetal weight is believed to emerge during the latter half of pregnancy. Although recent evidence suggests that crown-rump length (CRL) and nuchal translucency (NT) measured at 11-14 weeks correlate with abnormal fetal growth, findings have been limited by dating accuracy in spontaneous gestations. Therefore, we sought to determine whether CRL or NT measurements correlated with term birth weight (BW) or BW ratio in a cohort of IVF pregnancies, in which the date of conception is precisely known. This retrospective cohort study included 227 term, singleton IVF pregnancies. Subjects were included if they had an early first-trimester ultrasound examination and subsequent nuchal translucency (NT) screening. The difference between the measured and the expected CRL and the biparietal diameter (BPD) and NT measurement were calculated and correlated with the actual term BW or BW ratio. The BW ratio was calculated using the actual BW and the expected BW for GA. The difference between measured and expected mid-first-trimester CRL, and the BPD at NT assessment, correlated with BW ratio at delivery (rSpearman = 0.15, P = 0.023 and rSpearman = 0.27, P < 0.001, respectively). Absolute NT measurements and NT percentiles (adjusted for CRL) correlated with BW ratio at delivery (rSpearman = 0.18, r = 0.14, and P = 0.005 and 0.038, respectively). In this well-dated IVF population, we report a significant correlation between BW ratio and first-trimester CRL, BPD, and NT measurements. These findings support the hypothesis that physiological variation in BW can be reflected by variation in first-trimester fetal measurements.


Raynaud's phenomenon: a common toxicity after combination chemotherapy for testicular cancer.
Raynaud's phenomenon occurred in 22 of 60 men (37%) treated with vinblastine and bleomycin with or without cisplatin for germ cell testicular cancer. An additional six patients (10%) had symptoms suggestive of Raynaud's phenomenon. Patients with and without Raynaud's phenomenon did not differ with respect to median age; tumor histology; total doses of vinblastine, bleomycin, and cisplatin; or the frequency of vinblastine-induced neuropathy and bleomycin-induced cutaneous toxicity. Digital ischemia occurred in 21% of patients treated with only vinblastine and bleomycin, and in 41% of patients treated also with cisplatin. Cigarette smoking was commoner in patients with than in those without Raynaud's phenomenon. Hand arteriograms showed diffuse arterial narrowing and abrupt vascular cutoffs. Except for one patient with a very low titer of cold agglutinins, no patient had detectable antinuclear antibody, rheumatoid factor, cryoglobulins, or cold agglutinins. Raynaud's phenomenon is a common delayed toxicity after chemotherapy with vinblastine, bleomycin, and cisplatin in patients with germ cell neoplasms.


Familial Mediterranean fever and membranous glomerulonephritis: report of a case.
Familial Mediterranean fever (FMF) is an autosomal recessive genetic disease characterized by recurrent attacks of fever and painful episodes of sterile polyserositis. Kidney involvement may occur as a result of secondary amyloidosis during the course of FMF. Previously, different types of glomerulopathies such as IgM and IgA nephropathy, crescentic glomerulonephritis, diffuse proliferative glomerulonephritis, minimal change disease, and membranoproliferative glomerulonephritis were rarely reported. We herein represent a first case of membranous glomerulonephritis who had complete remission with colchicine treatment in the course of familial Mediterranean fever.


Are there disparities in acute stroke treatment between the Jewish and Arab populations in Israel? Results from the National Acute Stroke Israeli registry.
According to the latest reported data from the National Acute Stroke Israeli Survey (NASIS), around 18,000 strokes occur annually in Israel. Data regarding disparities in stroke care between the Jewish and the Arab populations in Israel are lacking. We wished to compare demographics, comorbidities, stroke characteristics and outcomes between Jewish and Arab stroke patients in Israel that were acutely treated with intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT), in order to test if there are disparities or any ethnic-specific parameters. The National Acute Stroke Israeli registry of patients undergoing revascularization (NASIS-REVASC) prospectively enrolled patients in six comprehensive stroke centers between 1/2014 and 3/2016. In this observational research, we compared demographics, comorbidities, time metrics, stroke characteristics and outcomes between Jewish and Arab patients enrolled. NASIS-REVASC included 1432 patients out of which 143 (10%) were of Arab ethnicity and 1289 (90%) of Jewish ethnicity. Arab patients were significantly younger (66 ± 14 vs. 73 ± 29, p = 0·004), exhibited higher rates of smoking and diabetes (31% vs. 18% and 57% vs. 34%, p < 0·001 for both), and were less often treated with systemic thrombolysis (48% vs. 59%, p = 0·012). However, the rates of any interventional treatment with either intravenous thrombolysis or endovascular thrombectomy as well as the rates of favorable outcomes and mortality were comparable between groups. Despite several baseline differences between Arab and Jewish Israeli stroke patients, treatment allocations, survival and functional outcomes were similar indicating lack of disparity in stroke care among patients treated acutely with IVT and/or EVT in Israel. Full data is available following a formal request to the NASIS-REVASC registry at the Israeli Health Ministry.


Variations in Macrophage Activation Syndrome-associated Cardiac Diseases: A Report on Two Cases.
Macrophage activation syndrome (MAS), a secondary hemophagocytic lymphohistiocytosis characterized by an excessive systemic inflammatory response, is a life-threatening and rare disease. Cardiovascular damage is a common and severe complication of the disease, however, it is easily ignored and not well studied. Herein, we report two cases of patients with MAS-associated heart damage and review the clinical characteristics, mechanism, and treatment. Case 1 along with systemic lupus erythematosus and Kikuchi necrotizing lymphadenitis occurred in fatal acute heart failure, and case 2 complicated adult-onset Still's Disease began with atrial fibrillation and had some improvement with the treatment of high dose corticosteroids. MAS-associated heart damage is a critical issue in clinical settings, and the etiology and mechanisms of MAS-associated cardiovascular diseases are likely multifactorial. The manifestations were various and high levels of the cytokines and cardiac damage may contribute to poor prognosis. Therefore, early intensive immunosuppressive therapy probably improves the treatment outcome.


[Cardiovascular risk factors in workers of oil and gas extraction enterprises].
The article deals with data on levels of biochemical markers of response to chemical risk factors (benzol, toluene) of cardiovascular diseases in workers engaged into oil and gas extraction. Findings are reliable differences between the workers groups in serum benzol and toluene levels, in classic biochemical effect markers of cardiovascular diseases (total cholesterol level, low density lipoproteins, uric acid), in activity of lipid peroxidation products deteriorating endothelial dysfuction.


[Hyperendemicity of human fasciolosis in the Mantaro Valley, Peru: factors for infection with Fasciole hepatica].
A sample of 206 children (between 1 and 16 years-old) in Huertas (n = 110) and Julcán (n = 96) districts of the Mantaro Valley, Peru, were studied with a clinico-epidemiological interview, serology and fecal parasitologic tests to describe the prevalence and analyze risk factors of infection by Fasciola hepatica (Fh). Fh prevalence by fecal examinations in Huertas (H) was 28.3% and Julcán (J), 12.6%. Using serological tests, the prevalences were: for H, 36.3% and for J, 22.7%. Univariate analysis showed a significant association between Fh infection and 3 variables in H: living near small streams (OR= 4.8; P < 0.05) or farms (OR= 2.88; P < 0.05) and the habit of drinking hot herbal drinks "emolientes" (OR= 2.92; P < 0.05); and in other 3 variables in J: having a single room per house (OR= 21.0; P < 0.05), defecating in the fields (OR= 4.77; P < 0.05), history of taking antiparasitic medication in the last six months (OR= 4.61; P < 0.05). Multivariate analysis, applied to the whole set of data revealed as possible risk factors for infection with Fh: the habit of drinking "emolientes" (OR= 5.16; P < 0.05) and living near small streams (OR= 17.22; P < 0.05) or in farms (OR= 8.13; P < 0.05). According to these results one of the most important and less recognized risk factors is the habit of drinking "emolientes". Due to the clinical importance of human fascioliasis, we conclude that its presence in the Mantaro Valley is an important public health problem, effective early diagnosis would allow rapid treatment and avoidance of the serious impairment brought by chronic infection.


Induction of heme oxygenase-1 expression inhibits platelet-dependent thrombosis.
Heme oxygenase-1 (HO-1) plays a key role in protecting tissue from oxidative stress. Although some studies implicate HO-1 in modulating thrombosis after vascular injury, the impact of HO-1 on the rate of clot formation in vivo is poorly defined. This study examined the potential function of HO-1 in regulating platelet-dependent arterial thrombosis. Platelet-rich thrombi were induced in C57BL/6J mice by applying 10% ferric chloride to the exposed carotid artery. Mean occlusion time of wild-type mice (n = 10) was 14.6 +/- 1.0 min versus 12.9 +/- 0.6 min for HO-1-/- mice (n = 11, p = 0.17). However, after challenge with hemin, mean occlusion time was significantly longer in wild-type mice (16.3 +/- 1.2 min, n = 15) than HO-1-/- mice (12.0 +/- 1.0 min, n = 9; p = 0.021). Hemin administration induced an approximately twofold increase in oxidative stress, measured as plasma thiobarbituric acid reactive substances. Immunohistochemical analysis revealed that hemin induced a robust increase in HO-1 expression within the carotid arterial wall. Ex vivo blood clotting within a collagen-coated perfusion chamber was studied to determine whether the accelerated thrombosis observed in HO-1-/- mice was contributed to by effects on the blood itself. Under basal conditions, mean clot formation during perfusion of blood over collagen did not differ between wild-type mice and HO-1-/- mice. However, after hemin challenge, mean clot formation was significantly increased in HO-1-/- mice compared with wild-type controls. These results suggest that, under basal conditions, HO-1 does not exert a significant effect on platelet-dependent clot formation in vivo. However, under conditions that stimulate HO-1 production, platelet-dependent thrombus formation is inhibited by HO-1. Enhanced HO-1 expression in response to oxidative stress may represent an adaptive response mechanism to down-regulate platelet activation under prothrombotic conditions.


Knowledge, attitude and practice towards pharmacovigilance among ayurveda physicians and teachers of Gujarat State: A cross sectional study.
The aim of this study was to assess the knowledge, attitude, and practice towards pharmacovigilance for Ayurveda among the teachers and practitioners working in Ayurveda colleges of Gujarat State. A survey questionnaire with 29 questions covering points like participants' knowledge, attitude and practice towards pharmacovigilance, adverse drug reaction reporting, and misleading advertisements related Ayurveda drugs was developed in Google form format. The study was carried out during December 2020 and January 2021. Question-wise analysis was made and their percentage value was calculated with the help of a Microsoft Excel spreadsheet in MS Office 2010. The result was presented using simple frequencies with percentages in appropriate tables. Results from this study show that majority of the respondents were having a good knowledge regarding the concept of pharmacovigilance and ADRs in terms of their definitions and purposes. But, a complete knowledge regarding the structure of present national and international pharmacovigilance programme, reporting the ADR and its format were still lacking among majority of the participants. An encouraging attitude towards reporting of adverse drug reaction of ASU&H drugs and teaching of Pharmacovigilance for all the healthcare professionals by majority of the participants was observed. Further maximum participants opine a mandatory rule for reporting of ADR by Physicians, Pharmacist and Nursing staff. A major part of respondents (78.03%) opine that poor quality of drug, medication errors, prescription errors, dispensing errors are part of Pharmacovigilance under drug-related problems. The observed positive attitude is not being reflected in term of practice i.e., reporting of ADR related to Ayurveda drugs. One-third of the participants reported their experience about adverse drug reactions during their professional practice, out of which very few have reported ADRs. Difficulty in deciding or identifying the ADR and lack of time to report ADR is one of the major factor discouraging the participants from reporting ADRs. A large number of respondents were also not familiar with reporting misleading advertisements. Findings of this study reflects a good knowledge of the participants about the concept of Pharmacovigilance but unfamiliarity about the programme. The positive attitude towards practice of Pharmacovigilance and ADR reporting can be converted to foster pharmacovigilance practice through series of awareness programmes.


[Boosted protease inhibitor monotherapy in HIV-infected patients: results of a study in a real life setting].
Boosted protease inhibitor monotherapy may offer antiviral efficacy while reducing drug interactions, costs and toxicity. The aim of this study was to assess the efficacy of darunavir/ritonavir (DRV/r) and lopinavir/ritonavir (LPV/r) monotherapy in a real life setting. A retrospective analysis of all HIV infected patients, who had initiated DRV/r or LPV/r monotherapy, was performed. Patients whose HIV viral load had remained undetectable for at least two consecutive follow-up visits and who had no neurocognitive disorder or hepatitis B co-infection, were included. Sixty patients were included. The median (IQR) time to follow-up was 66 (33-118) weeks. The proportions (CI95%) of patients with virological failure were 6.3% (1.7- 20.2) and 25.0% (12.7-43.4), respectively, in the DRV/r and LPV/r groups (p= 0.0424). The proportions (CI95%) of patients with therapeutic success were 90.6% (80.5-100) in the DRV/r group and 60.7% (42.6-78.8) in the LPV/r group (p=0.0063). No protease inhibitor mutations were detected. During the follow-up, 6 patients with dyslipidemia normalized their lipid values. The median monthly cost was 410 (IQR 242-416) euros per person lower for the monotherapy than for the combined antiretroviral therapy. Boosted protease inhibitor monotherapy was effective in a real life setting. This study showed differences in favour of DRV/r as compared with LPV/r in terms of therapeutic success; however prospective studies are needed to confirm these results. Finally, although this study was not specifically designed to detect benefits in terms of costs and lipid profile, it shows evidence of a positive impact of monotherapy in these fields.


Biocontrol Potential of Neoseiulus californicus (Mesostigmata : Phytoseiidae) Against Oligonychus punicae (Acari: Tetranychidae) in Avocado.
Oligonychus punicae (Hirst) (Trombidiformes: Tetranychidae) is a common pest in Mexican avocado orchards. Neoseiulus californicus (McGregor) (Mesostigmata: Phytoseiidae) is frequently found associated with avocado orchards in Mexico and may be an important aid for controlling O. punicae. Given the lack of information in the scientific literature, this study evaluated the predation and oviposition of N. californicus when fed O. punicae at different developmental stages in a no-choice experiment. We also assessed fluctuations in the population size of O. punicae and N. californicus in commercial avocado orchards; correlations among mite density and air temperature, humidity, and precipitation in commercial avocado orchards; and the correlations between prey and predator populations. The no-choice test revealed that N. californicus adult females fed on O. punicae of all developmental stages, with higher levels of predation being recorded for eggs, followed by larvae. The highest oviposition values of N. californicus females were observed when females were fed O. punicae eggs. In orchards, the populations of both mites increased between February and June. The populations peaked during the warmest months of the year, with O. punicae populations peaking between June and July and N. californicus peaking in August. In addition, the population size of N. californicus was significantly and positively correlated with rainfall, air temperature, and the population densities of O. punicae. Meanwhile, O. punicae population size was positively correlated with air temperature, and the population of its predator N. californicus.


Through Thick and Thin: a Need to Reconcile Contradictory Results on Trajectories in Human Cortical Development.
Understanding how brain development normally proceeds is a premise of understanding neurodevelopmental disorders. This has sparked a wealth of magnetic resonance imaging (MRI) studies. Unfortunately, they are in marked disagreement on how the cerebral cortex matures. While cortical thickness increases for the first 8-9 years of life have repeatedly been reported, others find continuous cortical thinning from early childhood, at least from age 3 or 4 years. We review these inconsistencies, and discuss possible reasons, including the use of different scanners, recording parameters and analysis tools, and possible effects of variables such as head motion. When tested on the same subsample, 2 popular thickness estimation methods (CIVET and FreeSurfer) both yielded a continuous thickness decrease from 3 years. Importantly, MRI-derived measures of cortical development are merely our best current approximations, hence the term "apparent cortical thickness" may be preferable. We recommend strategies for reaching consensus in the field, including multimodal neuroimaging to measure phenomena using different techniques, for example, the use of T1/T2 ratio, and data sharing to allow replication across analysis methods. As neurodevelopmental origins of early- and late-onset disease are increasingly recognized, resolving inconsistencies in brain maturation trajectories is important.


Incidence and nature of human tuberculosis due to Mycobacterium africanum in South-East England: 1977-87.
A total of 210 new cases of tuberculosis due to Mycobacterium africanum were registered at the South-East Regional Centre for Tuberculosis Bacteriology, Dulwich, between 1977 and 1987 inclusive. This represented 1.25% of bacteriologically-confirmed cases of tuberculosis in South-East England, an incidence slightly higher than that of disease due to M. bovis. Two variants were identified: 150 strains were typed as African I (a type associated with East Africa) and 60 as African II (a type more prevalent in West Africa). Over half the patients infected with African I strains were of Indian subcontinent ethnic origin; patients of African ethnic origin predominated in the African II group while about a fifth o patients infected with either type were of European origin. The European patients with tuberculosis due to M. africanum were notably younger than those in the same region with disease due to other tubercle bacilli. The distribution of lesions due to M. africanum was similar to that due to other tubercle bacilli in the various ethnic groups, except that genito-urinary tuberculosis was uncommon. The importance of a clinical awareness that M. africanum is a highly pathogenic and transmissible tubercle bacillus rather than an opportunist or 'atypical' mycobacterium is stressed.


Measuring emotion socialization in families affected by pediatric cancer: Refinement and reduction of the Parents' Beliefs about Children's Emotions questionnaire.
The aim of this study is to conduct a multimethod psychometric reduction in the Parents' Beliefs about Children's Emotions (PBCE) questionnaire using an item response theory framework with a pediatric oncology sample. Participants were 216 pediatric oncology caregivers who completed the PBCE. The PBCE contains 105 items (11 subscales) rated on a 6-point Likert-type scale. We evaluated the PBCE subscale performance by applying a partial credit model in WINSTEPS. Sixty-six statistically weak items were removed, creating a 44-item PBCE questionnaire with 10 subscales and 3 response options per item. The refined scale displayed good psychometric properties and correlated .910 with the original PBCE. Additional analyses examined dimensionality, item-level (e.g. difficulty), and person-level (e.g. ethnicity) characteristics. The refined PBCE questionnaire provides better test information, improves instrument reliability, and reduces burden on families, providers, and researchers. With this improved measure, providers can more easily identify families who may benefit from psychosocial interventions targeting emotion socialization. The results of the multistep approach presented should be considered preliminary, given the limited sample size.


Immunosuppressive macrophages induced by IDO1 promote the growth of endometrial stromal cells in endometriosis.
It was previously demonstrated that anomalous expression of indoleamine 2,3-dioxygenase-1 (IDO1) in endometrial stromal cells (ESCs) stimulated an inflammatory response that subsequently initiated the activation of immunosuppressive macrophages in endometriosis. The aim of the present study was to clarify the effect of IDO1‑induced macrophages on the growth of ESCs in endometriosis. Normal ESCs, ectopic ESCs and normal ESCs treated with plasmid pEGFP‑N1‑IDO1 or SD11‑IDO1 short hairpin RNA were co‑cultured with peripheral blood‑derived monocyte (PBMC)‑driven macrophages directly for 48 h. Compared with normal ESCs, the PBMC‑driven macrophages that were co‑cultured with ectopic ESCs displayed a lower phagocytic ability. pEGFP‑N1‑IDO1 transfection of normal ESCs also decreased the phagocytic ability of co‑cultured macrophages. Additionally, pEGFP‑N1‑IDO1‑transfected ESC‑induced macrophages significantly increased the viability and proliferation of ESCs, while ESC apoptosis was decreased, compared with control ESCs. In conclusion, IDO1 educated-macrophages may facilitate the survival of retrograde endometrial tissues, and be involved in the pathogenesis of endometriosis.


Imaging findings of pancreatic cystic lesions in von Hippel-Lindau disease.
The aim of this study was to characterize the pancreatic cystic lesions in von Hippel-Lindau (VHL) disease and to document the changes that occur in the pancreas. We retrospectively analyzed the medical records and the computed tomography (CT) and magnetic resonance imaging (MRI) findings of 20 VHL patients who were diagnosed between 1996 and 2010 at our hospital. The clinical findings, family history and type of tumors and/or cysts were reviewed for each patient. We also analyzed the imaging findings for the pancreas in detail. Pancreatic involvement was noted in 16 of the 20 patients (80%). Eleven patients had multiple cysts diffusely distributed in the pancreas, and one patient had a single cyst in the pancreas head. Two patients had serous cystic neoplasms (SCNs) with multiple cysts, and another two patients had neuroendocrine tumors (NETs) which were conventional radiological findings. The largest cysts of four patients (26.7%) increased in size and that of three patients (20%) decreased in size during the follow-up period. We performed surgical resections for the pancreatic tumors (one NET and one SCN) and also performed endoscopic treatment for a pancreatic cyst in one VHL patient with obstructive jaundice. None of the patients died as a result of pancreatic disease. The most common type of pancreatic lesions was multiple cysts. SCNs were present in only 10% of the VHL patients. Pancreatic cysts showed positive and/or negative growth according to the CT and MRI findings. The pancreatic cystic lesions did not influence the outcome of the VHL patients.


Integration of genome and transcriptome reveal molecular regulation mechanism of early flowering trait in Prunus genus (Prunus mume and Prunus persica).
Flowering time is crucial for the survival and reproduction. Prunus genus belongs to the Rosaceae family and includes several hundred species of flowering trees and shrubs with important ornamental and economic values. However, the molecular mechanism underlying early flowering in Prunus genus is unclear. Here, we utilized the genome and transcriptome of P. mume and P. persica to explore the transcriptional regulation mechanism of early flowering. Comparative genomics found that genes accounting for 92.4% of the total P. mume genome and 91.2% of the total P. persica genome belonged to orthogroups. A total of 19,169 orthogroups were found between P. mume and P. persica, including 20,431 corresponding orthologues and 20,080 collinearity gene pairs. A total of 305 differentially expressed genes (DEGs) associated with early flowering were found, among which FT, TLI65, and NAP57 were identified as hub genes in the early flowering regulation pathway. Moreover, we identified twenty-five transcription factors (TFs) from nine protein families, including MADS-box, AP2/ERF, and MYB. Our results provide insights into the underlying molecular model of flowering time regulation in Prunus genus and highlight the utility of multi-omics in deciphering the properties of the inter-genus plants.


TBAI-Mediated Cyclization and Methylsulfonylation of Propargylic Amides with Dimethyl Sulfite.
A tetramethylammonium iodide (TBAI)-mediated cyclization and methylsulfonylation of propargylic amides enabled by dimethyl sulfite as a SO2 surrogate and methyl source have been developed. The transition metal-free and oxidant-free reaction provides a practical and efficient approach for the selective synthesis of methylsulfonyl oxazoles in moderate to excellent yields with good functional group compatibility.


Functional characteristics of the bovine hypothalamic-pituitary-adrenal axis vary with temperament.
Hypothalamic-pituitary-adrenal (HPA) axis function, in Brahman heifers of differing temperament, was evaluated using separate challenges with CRH and ACTH. Exit velocity (EV) measurement was used to classify heifer temperament as calm [C; consisted of 6 slowest heifers (EV=1.05+/-0.05 m/s)] or temperamental [T; 6 fastest heifers (EV=3.14+/-0.22 m/s)]. During the 6 h prior to CRH challenge, areas under the ACTH (P=0.025) and cortisol (P<0.001) curves were greater in the temperamental heifers. Baseline cortisol (P<0.001) but not ACTH (P=0.10) differed between temperament groups. Following CRH challenge, areas under the ACTH (P=0.057) and cortisol (P<0.01) response curves were greater in the calm animals. The same animals were subjected to an ACTH challenge 14 d following their utilization in the CRH stimulation experiment. Prior to ACTH challenge, baseline cortisol concentrations were higher (P<0.001) in the temperamental heifers (T=18+/-2.6, C=4.3+/-0.6 ng/mL). Following ACTH administration, area under the cortisol response curve was greater (P=0.07) in the calm heifers. After declining below baseline concentrations during the post-challenge recovery period, cortisol in temperamental animals was again greater (P=0.02) than in the calm heifers. These data demonstrate that cattle with an excitable temperament exhibit increased stress responsiveness to handling, increased baseline adrenal function but not increased basal pituitary function, and a muted responsiveness to pharmacological stimulus. Thus, functional characteristics of the HPA axis vary with animal temperament.


Molecular representation of molar domain (volume), evolution equations, and linear constitutive relations for volume transport.
In the traditional theories of irreversible thermodynamics and fluid mechanics, the specific volume and molar volume have been interchangeably used for pure fluids, but in this work we show that they should be distinguished from each other and given distinctive statistical mechanical representations. In this paper, we present a general formula for the statistical mechanical representation of molecular domain (volume or space) by using the Voronoi volume and its mean value that may be regarded as molar domain (volume) and also the statistical mechanical representation of volume flux. By using their statistical mechanical formulas, the evolution equations of volume transport are derived from the generalized Boltzmann equation of fluids. Approximate solutions of the evolution equations of volume transport provides kinetic theory formulas for the molecular domain, the constitutive equations for molar domain (volume) and volume flux, and the dissipation of energy associated with volume transport. Together with the constitutive equation for the mean velocity of the fluid obtained in a previous paper, the evolution equations for volume transport not only shed a fresh light on, and insight into, irreversible phenomena in fluids but also can be applied to study fluid flow problems in a manner hitherto unavailable in fluid dynamics and irreversible thermodynamics. Their roles in the generalized hydrodynamics will be considered in the sequel.


[Recent oral antidiabetic therapy].
The improvement of the diabetic equilibrium decreases the microvascular complications. Unfortunately, the HbA1c has tendency to increase with time and too few type 2 diabetic patients are well equilibrated with HbA1c under 7%. We have now new medicaments to improve this. The thiazolidinediones are agonists of the PPARgamma and ameliorate the insulin resistance with decrease of the HbA1c. Pioglitazone (Actos) and rosiglitazone (Avandia) are the two thiazolidinediones in Belgium. To be reimbursed, these medicaments have to be prescribed with sulfonylureas or metformin. The glinides are secretagogues drugs acting on the post-prandial glycaemia, but they improve the three parameters of diabetic equilibrium: fasting glycaemia, postprandial glycaemia and HbA1c. There is only one in Belgium: repaglinide (Novonorm). We can also improve the treatment by increasing the compliance. Therefore we can prescribe treatment with once daily dosage so as glimepiride (Amarylle) or gliclazide MR (Unidiamicron). Finally there are 'fixed combinations of two molecules so as glibenclamide + metformin (Glucovance) or rosiglitazone + metformin (Avandamet).


[Gastric emptying of solids in patients with nonorganic dyspepsia].
The purpose of this work was to evaluate gastric emptying of a solid meal in 20 patients with functional dyspepsia and in 20 healthy controls. Gastric emptying time (T 1/2 = 188.45 +/- 93.79; p less than 0.001 - E.I. = 0.43 +/- 0.16; p less than 0.001) was significantly delayed in patients with functional dyspepsia compared with controls. The conclusion is drawn that either antral motor activity or antral-pyloric-duodenal motor activity is impaired in such patients.


Occult Pneumomediastinum in the Deployed Setting: Evaluation and Management.
Pneumomediastinum can occur after both blunt and penetrating trauma. The greatest concern involving this finding in a trauma patient is an aerodigestive tract injury. Prompt evaluation, identification, and management of these injuries are extremely important. This case describes a soldier who was involved in an improvised explosive device blast with no evidence of cavity penetration. During the routine evaluation of his head and neck an occult pneumomediastinum was identified. The patient was asymptomatic and was further evaluated with computed tomography because of the absence of endoscopy and bronchoscopy in theatre. The imaging showed no evidence of esophageal or tracheobronchial injury. The patient was observed and when noted to be stable was transferred to the local Role 3 hospital for management of his other injuries.


Photoluminescent and Scintillating Performance of Eu3+-Doped Boroaluminosilicate Glass Scintillators.
In comparison with single crystal scintillators, glass scintillators are more promising materials for their benefits of easy preparation, low cost, controllable size, and large-scale manufacture. The emission of Eu3+ ion at 612 nm matches well with the photoelectric detector, making it suitable for the activator in glass scintillators. Therefore, the research on Eu3+ doped glass scintillators attract our attention. The photoluminescent and scintillating properties of Eu3+-activated boroaluminosilicate glass scintillators prepared by the conventional melt-quenching method were investigated in this work. The glass samples present good internal quantum yield. Under X-ray radiation, the optimal sample reveals high X-ray excited luminesce (XEL), and its integrated intensity of XEL is 22.7% of that of commercial crystal scintillator Bi4Ge3O12. Furthermore, the optimal specimen possesses a spatial resolution of 14 lp/mm in X-ray imaging. These results suggest that Eu3+-doped boroaluminosilicate glass is expected to be applied in X-ray imaging.


Changes in levels of apoptosis in the walls of different segments of great saphenous varicose veins.
Disordered programmed cell death may play a role in the development of superficial venous incompetence. We have determined the number of cells undergoing apoptosis and the alterations in the apoptotic level in the wall of different segments of the great saphenous varicose vein. Twenty-one varicose great saphenous veins (VGSVs) (varicose group) and 12 normal great saphenous veins (GSVs) (control group) were collected, and the apoptosis level in the upper, middle, and lower segments were immunohistochemically stained with antibodies (anti-Bax and anti-Bcl-xl). Apoptosis was evaluated by the TUNEL assay and immunofluorescence staining. The morphology of apoptotic cells was observed with an electron microscope. Quantitative analysis showed that the apoptotic ratios in venous walls (intima and media) of the varicose group were significantly lower than the corresponding regions in the control group (all P < 0.05). A significantly higher apoptotic rates of the venous walls was observed in control group within the upper compared with the lower segment (P < 0.05). Significantly higher positive proteins expression rates of Bcl-xl/Bax were also detected in the VGSVs compared with the GSVs within the three segments, respectively (P < 0.01). Electron microscopic observations confirmed that endothelial and smooth muscle cells in varicose and normal vein walls exhibited apoptotic morphologic features, such as fuzzy mitochondrial cristae, medullary changes, and margination of the nuclear chromatin. VGSV walls were found to have a significant decrease in apoptotic rate compared with that of GSVs. The rate of apoptosis in the intima and media within the upper segment was increased more than the middle and lower segments in the GSVs. Our findings confirm that programmed cell death is down-regulated in primary varicose veins.


Genetic Diversity, Population Structure, and Linkage Disequilibrium of an Association-Mapping Panel Revealed by Genome-Wide SNP Markers in Sesame.
The characterization of genetic diversity and population structure can be used in tandem to detect reliable phenotype-genotype associations. In the present study, we genotyped a set of 366 sesame germplasm accessions by using 89,924 single-nucleotide polymorphisms (SNPs). The number of SNPs on each chromosome was consistent with the physical length of the respective chromosome, and the average marker density was approximately 2.67 kb/SNP. The genetic diversity analysis showed that the average nucleotide diversity of the panel was 1.1 × 10-3, with averages of 1.0 × 10-4, 2.7 × 10-4, and 3.6 × 10-4 obtained, respectively for three identified subgroups of the panel: Pop 1, Pop 2, and the Mixed. The genetic structure analysis revealed that these sesame germplasm accessions were structured primarily along the basis of their geographic collection, and that an extensive admixture occurred in the panel. The genome-wide linkage disequilibrium (LD) analysis showed that an average LD extended up to ∼99 kb. The genetic diversity and population structure revealed in this study should provide guidance to the future design of association studies and the systematic utilization of the genetic variation characterizing the sesame panel.


SAR11 Cells Rely on Enzyme Multifunctionality To Metabolize a Range of Polyamine Compounds.
In the ocean surface layer and cell culture, the polyamine transport protein PotD of SAR11 bacteria is often one of the most abundant proteins detected. Polyamines are organic cations at seawater pH produced by all living organisms and are thought to be an important component of dissolved organic matter (DOM) produced in planktonic ecosystems. We hypothesized that SAR11 cells uptake and metabolize multiple polyamines and use them as sources of carbon and nitrogen. Metabolic footprinting and fingerprinting were used to measure the uptake of five polyamine compounds (putrescine, cadaverine, agmatine, norspermidine, and spermidine) in two SAR11 strains that represent the majority of SAR11 cells in the surface ocean environment, "Candidatus Pelagibacter" strain HTCC7211 and "Candidatus Pelagibacter ubique" strain HTCC1062. Both strains took up all five polyamines and concentrated them to micromolar or millimolar intracellular concentrations. Both strains could use most of the polyamines to meet their nitrogen requirements, but polyamines did not fully substitute for their requirements of glycine (or related compounds) or pyruvate (or related compounds). Our data suggest that potABCD transports all five polyamines and that spermidine synthase, speE, is reversible, catalyzing the breakdown of spermidine and norspermidine, in addition to its usual biosynthetic role. These findings provide support for the hypothesis that enzyme multifunctionality enables streamlined cells in planktonic ecosystems to increase the range of DOM compounds they metabolize. IMPORTANCE Genome streamlining in SAR11 bacterioplankton has resulted in a small repertoire of genes, yet paradoxically, they consume a substantial fraction of primary production in the oceans. Enzyme multifunctionality, referring to enzymes that are adapted to have broader substrate and catalytic range than canonically defined, is hypothesized to be an adaptation that increases the range of organic compounds metabolized by cells in environments where selection favors genome minimization. We provide experimental support for this hypothesis by demonstrating that SAR11 cells take up and metabolize multiple polyamine compounds and propose that a small set of multifunctional enzymes catalyze this metabolism. We report that polyamine uptake rates can exceed metabolic rates, resulting in both high intracellular concentrations of these nitrogen-rich compounds (in comparison to native polyamine levels) and an increase in cell size.


Gonadal steroids as promoters of neuro-glial plasticity.
Estradiol induces coordinated modifications in the extension of glial and neuronal processes in the arcuate nucleus of the hypothalamus of adult female rats. This hormonal effect results in natural fluctuations in the ensheathing of arcuate neurons by glial processes and these glial changes are linked to a remodelling of inhibitory GABAergic synapses during the estrous cycle. Hormonally induced glial and synaptic changes appear to be dependent on specific recognition or adhesion molecules on the neuronal and/or glial membranes.


Very low concentrations of ethanol suppress excitatory synaptic transmission in rat visual cortex.
Ethanol is one of the most commonly used substances in the world. Behavioral effects of alcohol are well described, however, cellular mechanisms of its action are poorly understood. There is an apparent contradiction between measurable behavioral changes produced by low concentrations of ethanol, and lack of evidence of synaptic changes at these concentrations. Furthermore, effects of ethanol on synaptic transmission in the neocortex are poorly understood. Here, we set to determine effects of ethanol on excitatory synaptic transmission in the neocortex. We show that 1-50 mm ethanol suppresses excitatory synaptic transmission to layer 2/3 pyramidal neurons in rat visual cortex in a concentration-dependent manner. To the best of our knowledge, this is the first demonstration of the effects of very low concentrations of ethanol (from 1 mm) on synaptic transmission in the neocortex. We further show that a selective antagonist of A1 adenosine receptors, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), blocks effects of 1-10 mm ethanol on synaptic transmission. However, the reduction in excitatory postsynaptic potential amplitude by 50 mm ethanol was not affected by DPCPX. We propose that ethanol depresses excitatory synaptic transmission in the neocortex by at least two mechanisms, engaged at different concentrations: low concentrations of ethanol reduce synaptic transmission via A1 R-dependent mechanism and involve presynaptic changes, while higher concentrations activate additional, adenosine-independent mechanisms with predominantly postsynaptic action. Involvement of adenosine signaling in mediating effects of low concentrations of ethanol may have important implications for understanding alcohol's effects on brain function, and provide a mechanistic explanation to the interaction between alcohol and caffeine.


Children and medical research.
A considerable proportion of medical treatments for children are based on estimates and assumptions rather than clinical evidence. Clinical research on children provokes intensive discussion internationally. While children are protected from the risks of clinical trials, they are hindered from receiving the benefits of pharmaceutical innovations obtained by adults. The recruitment of children into research trials is more complicated than that of adults for several reasons: 1) the physical size and relative water content of the body differs not just compared to adults but also amongst subgroups of children making the group of potential participants relatively small; 2) diseases common among adults may be rare among children and vice versa; 3) children's ability to understand the significance of a study varies and depends on the age and developmental stage of the child; and 4) depending on the level of understanding, differing views have been given on the degree of respect that should be paid to a child's right to consent, assent, or refuse to participate in a trial. We suggest that: 1) the number of children recruited in research trials should be kept as small as possible, but large enough to enable scientifically valid results; 2) special training should be made mandatory for researchers who study diseases of children; 3) children or adolescents should participate in decision-making that concerns them whenever possible; and 4) in minor procedures, the consent of just one parent is sufficient.


Determination and validity of critical swimming velocity in elite physically disabled swimmers.
The purpose of this investigation was to determine if the critical swimming velocity (CSV), defined as the theoretical maximal swimming velocity that could be maintained for a long period of time without exhaustion, corresponds to the exercise intensity at onset blood lactate accumulation (OBLA), and if it could be utilized as a practical index for assessing endurance performance in elite physically disabled swimmers. Eight elite physically disabled swimmers swam four different distances (50, 100, 200 and 400 m) at maximal effort. The swimming time was taken during each trial. The CSV was expressed as the slope of a regression line between the covered swimming distance and the corresponding times of all possible combinations of 2 or 4 time trials. Results indicate that all the CSVs calculated were similar independently of the distances utilized for their calculation. Afterwards, a CSV confirmation test consisting of 3 x 10-min trials at 95, 100, 105% of the CSV was carried out. The lactate concentration at the end of each trial was 3.32, 4.03 and 5.73 mmol x l(-1), respectively. Lactate concentration at 100% CSV approached the value of 4 mmol x l(-1), which is considered the exercise intensity at OBLA. We conclude that the CSV corresponds with the OBLA intensity and could be a valuable index to plan a training schedule for physically disabled swimmers.


Acute care of the high-level quadriplegic patient.
Four months post-injury, Mark is into the ongoing rehabilitation phase of his hospitalization. He is free of continuous ventilator support with a vital capacity of 1200 cc. Neurologically, his level has descended to the C5 level, which has allowed him to function with moderate assistance from a motorized wheelchair. He is still immobilized in a Halo vest which will be removed when X-ray examination reveals that adequate fusion has occurred. Mark has not developed pulmonary embolus. After an initial problem with orthostatic hypotension, he can sit upright without symptomatology. Although he will probably continue to have difficulty with temperature regulation, Mark has learned how to control his environment in order to maintain his comfort and safety. Bowel training was difficult because of Mark's initial problem with paralytic ileus. With persistent adherence to the bowel program, however, Mark has become bowel continent. This process was facilitated once he was able to be mobilized and use a bedside commode. Mark continues on his bladder retraining program. As could be anticipated with an adolescent patient, adherence to the strict program of fluid regulation and restriction was difficult. It is anticipated that Mark will eventually be catheter-free and bladder continent in the future. Mark will require two to three months of further rehabilitation, after which he will return to his home and school. Mark faces a future centered from a wheelchair. With adequate medical, nursing, psychological, social and vocational follow-up, however, he can live a near normal life-span. With a positive support system he can build on the comprehensive care he received initially, and rebuild a life for himself.


[Medicine and religion in Spanish anti-superstition discourse of the 16th to 18th centuries: a battle for hegemony].
The object of this research is the study of the different kinds of relationships between medicine and religion that appear in the Spanish anti-superstition discourse from the 16th to the 18th century. Despite the relationship of alliance and collaboration between the two professional groups proposed by the Spanish theologians in their essays, situations of conflict and mutual distrust could also arise. The professional physician could be an ally of the Christian priest but also a dangerous rival.


The Orthodontic Mini-Implants Failures Based on Patient Outcomes: Systematic Review.
Anchorage is a challenge and essential issue for an orthodontist in determining the success of orthodontic treatment. Orthodontic anchorage is defined as resistance to unwanted tooth movement. Mini-implant is one of the devices that can be used as an anchor in orthodontic treatment. Many cases have reported successful treatment using mini-implant, but there are cases where mini-implants may fail. Failure of mini-implants can affect orthodontic treatment, and it is known that several factors may lead to mini-implant loss in orthodontic treatment. This systematic review aimed to determine the factors influencing mini-implant failure in orthodontic treatment. Articles were selected from electronic databases (PubMed, Google Scholar, The Cochrane Library, ScienceDirect) from January 2015 until 2023 according to the PRISMA method (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) under the PEOS (Population-Exposure-Outcome-StudyType) framework questions for systematic review. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022337684). All data collected were in English, and filtering was done by eliminating duplicate data, meta-analysis, case reports, case series, mini-reviews, and animal studies. The analysis was further divided into three groups, that is, patient-related, implant-related, and operator-related and operator-related (A graphical abstract provided as a Supplementary information [available in the online version]). Twenty-one articles were identified according to the inclusion criteria in the form of retrospective, prospective, in vivo, and randomized controlled trial studies. Mini-implant failures due to patient-related showed six etiological factors, failures due to implant-related had eight etiological factors, and only one factor was operator-related, which may lead to mini-implant failure. The data was extracted without a computerized system and only in English. Mini-implant failure can be caused by many factors; we could not accuse one major factor as a cause. However, the quality or condition of the bones and oral hygiene are factors that play a significant role in obtaining the stability of implants. Mini-implant failure is highly influenced by poor oral hygiene and peri-implant inflammation. Comprehensive diagnostic prior to mini-implant insertion should be appropriately considered. This systematic review describes several factors that can influence mini-implant failure, divided into three groups: patient-related, implant-related, and operator-related (A graphical abstract provided as a Supplementary information [available in the online version]).


Intracranial suppuration 1968-1982--a 15 year review.
The CT scanner and the recognition of anaerobic organisms has altered the investigation and management of intracranial suppuration. Improved treatment of acute and chronic middle ear infection has also occurred. A 15 year retrospective review was undertaken to assess the effects of these changes. The ears and sinuses were confirmed as the major source of intracranial suppuration (69%) although initial presentation to ENT surgeons was less common (14%). Ear complications occur in childhood and in the fifth and sixth decades; sinus complications predominantly in the second and third decades. The incidence of sinus infection appears to be rising. With the introduction on the CT scanner cerebral abscess mortality declined from 27.5% to 6.5% and subdural abscess mortality halved. The introduction of metronidazole contributed to a drop in mortality. The use of the CT scanner and more accurate antibacterial treatment, including metronidazole, gives hope for a more successful outcome than was previously possible.


Metal-Oxides- and Metal-Oxyhydroxides-Based Nanocomposites for Water Splitting: An Overview.
Water electrolysis is an important alternative technology for large-scale hydrogen production to facilitate the development of green energy technology. As such, many efforts have been devoted over the past three decades to producing novel electrocatalysis with strong electrochemical (EC) performance using inexpensive electrocatalysts. Transition metal oxyhydroxide (OxH)-based electrocatalysts have received substantial interest, and prominent results have been achieved for the hydrogen evolution reaction (HER) under alkaline conditions. Herein, the extensive research focusing on the discussion of OxH-based electrocatalysts is comprehensively highlighted. The general forms of the water-splitting mechanism are described to provide a profound understanding of the mechanism, and their scaling relation activities for OxH electrode materials are given. This paper summarizes the current developments on the EC performance of transition metal OxHs, rare metal OxHs, polymers, and MXene-supported OxH-based electrocatalysts. Additionally, an outline of the suggested HER, OER, and water-splitting processes on transition metal OxH-based electrocatalysts, their primary applications, existing problems, and their EC performance prospects are discussed. Furthermore, this review article discusses the production of energy sources from the proton and electron transfer processes. The highlighted electrocatalysts have received substantial interest to boost the synergetic electrochemical effects to improve the economy of the use of hydrogen, which is one of best ways to fulfill the global energy requirements and address environmental crises. This article also provides useful information regarding the development of OxH electrodes with a hierarchical nanostructure for the water-splitting reaction. Finally, the challenges with the reaction and perspectives for the future development of OxH are elaborated.


The New HARMONIC ACE®+7 Shears: A Game Changer in Ultrasonic Hemostasis.
The latest version of HARMONIC®, the HARMONIC ACE®+7 Shears by Ethicon US, LLC, is now commercially available. While earlier models also had easy-to-use handles and a fine, non-stick tip, the HARMONIC ACE®+7 Shears adds a new hemostasis feature. The "7" in HARMONIC ACE®+7 stands for the device's ability to coagulate and divide 7-mm vessels. This is accomplished via an Advanced Hemostasis Mode and button located on both sides of the handle. The HARMONIC ACE®+7 will prove itself the leader in the ultrasonic energy field.


Low-dose quadruple antihypertensive combination: more efficacious than individual agents--a preliminary report.
Increasingly combined antihypertensive agents are being used in practice to enhance control and improve compliance. To determine whether a capsule containing a quarter of the standard dose of 4 antihypertensive agents has greater efficacy than the standard dose of each individually, we prospectively randomized 108 untreated white hypertensive patients (55% male) aged 50+/-1 years (mean+/-SEM), with mean blood pressure 160+/-1/96+/-1 mm Hg. Patients received amlodipine (5 mg; n=22), atenolol (50 mg; n=20), bendroflumethiazide (2.5 mg; n=22), captopril (50 mg twice daily; n=22) or a capsule containing each of the 4 above at one-quarter dosage (n=22) in a parallel group design for 4 weeks. Blood pressure was measured using a semiautomated device (Omron 705), and the reduction in mean arterial pressure with the combined preparation was compared with that of the individual components. Statistical analysis used ANOVA and Tukey-Kramer honestly significant difference for multiple comparisons. The reduction in mean arterial pressure with the combination (19+/-2 mm Hg) was significantly greater than that with individual agents amlodipine (10+/-2 mm Hg; P<0.005), atenolol (10+/-2 mm Hg; P<0.005), bendroflumethiazide (6+/-1 mm Hg; P<0.005), and captopril (11+/-1 mm Hg; P<0.01). In addition, the percentage reduction in systolic (18+/-1 mm Hg; P<0.005) and diastolic (17+/-2 mm Hg; P=0.06) blood pressure was greater with the combination. More patients achieved a blood pressure of <140/90 mm Hg with the combination (60%) than any individual drug (15% to 45%; P<0.05). A low-dose combination of 4 agents representing 4 classes of standard antihypertensive agents was more efficacious than a standard single dose of each agent individually.


Synthesis of optically active trans 4-cyclohexyl-L-proline as an intermediate product in the preparation of fosinopril.
A nine-step synthesis of trans 4-cyclohexyl-L-proline has been developed on a laboratory scale. The product is an intermediate in the preparation of fosinopril--an effective hypotensive drug. The total yield of the synthesis was 25%. The final product was 99.7% pure. Analytical methods were developed for each step of the synthesis (HPLC, TLC, IR, 1H-NMR, 13C-NMR, GC-MS, [alpha]D).


Synthesis and field emission properties of ultra-nanocrystalline diamond fibers and helices.
We propose a novel template method for large scale synthesis of Ultra-Nanocrystalline Diamond (UNCD) fibres and helices with lengths of thousands of microns and diameters ranging from 0.5 to 5 microm: (i) Large quantities of submicrometer- or nanometer-diameter silica (a-SiO2) nanostructures, with lengths in the order of 2 to 4 mm, were synthesized by Vapor-Liquid-Solid (VLS) method; (ii) UNCD coating of as-synthesized a-SiO2 micro- or nanonanostructures by Microwave Plasma Chemical Vapour Deposition (MPCVD) technique in hydrogen-deficient condition. Electron Field Emission (EFE) of as-synthesized UNCD structures was observed with a threshold field of 3.4 V/microm. These micro- or nanostructures may find potential applications in high power electronics, vertical field-effect transistors in vacuum electronics, heat sinks in microelectronics and structural materials in Micro- and Nano-Electro-Mechanical Systems (MEMS/NEMS). The successful preparation of various types of UNCD structures suggests that this templating process can be used for a wide range of materials.


Greywater treatment by granular filtration system using volcanic tuff and gravel media.
The main objective of this study was to evaluate the efficiency of a granular filtration system (GFS) in greywater treatment under arid and semi-arid conditions. Six GFSs were designed, constructed, and monitored for approximately 13 months. Each GFS served a single rural Jordanian home by treating their greywater. Volcanic tuff media were used as the filtration media in three of the GFSs while the remaining three GFSs used gravel media. Results show that the biological oxygen demand, chemical oxygen demand, and total suspended solids of the effluent were significantly lower as compared to the influent and demonstrated a removal efficiency of 73%, 65%, and 85%, respectively, when using volcanic tuff media. The removal efficiency was 49%, 51%, and 76%, respectively, when using gravel media. There was a significant increase in the electrical conductivity, pH, potassium (K+), magnesium (Mg2+), chloride (Cl-), sodium (Na+), sulfate (SO42-), bicarbonates (HCO3-), sodium adsorption ratio, and exchangeable sodium percentage in the effluents of the GFS that used volcanic tuff media. The study suggests that GFSs can adequately treat greywater under arid conditions. However, gravel media produce less concentrated effluent compared to the volcanic tuff media.


[Skeletal changes following long-term treatment with retinoids].
The synthetic retinoids, the vitamin-D-derivatives etretinate and isotretinoin, have substantially enlarged the therapeutic arsenal in dermatology. They are primarily used in severe cases of acne and cornification disorders. In the majority of cases, long-term treatment is necessary. Certain side effects in the skeletal system can occur, e.g., osteoporosis, premature epiphyseal closure, and changes similar to DISH (diffuse idiopathic skeletal hyperostosis). We discuss the reports in the literature and our own observations in 31 patients treated at the Westphalian Wilhelms University in Muenster, as well as at the Technical University in Munich. In 3 out of 31 patients treated by retinoids on a long-term basis, skeletal changes were found radiologically as a result of the retinoid medication.


Autologous Fat Graft for the Treatment of Sighted Posttraumatic Enophthalmos and Sunken Upper Eyelid.
The treatment of enophthalmos and sunken upper eyelid is challenging. Although autologous fat graft has been widely used in breast augmentation, buttock contouring, and facial rejuvenation, its application in enophthalmos and sunken upper eyelid is not yet widely utilized. The clinical safety and value of autologous fat graft in sighted patients with enophthalmos and sunken upper eyelid are unclear. This study retrospectively analyzed the cosmetic results and safety of autologous fat graft in the correction of sighted traumatic enophthalmos and sunken upper eyelid. Autologous fat graft was performed in 9 patients with posttraumatic enophthalmos and sunken upper eyelid. The visual acuity, orbital swelling, eye movement, enophthalmos, and sunken upper eyelid were observed. Eight to 24 months after autologous fat graft, enophthalmos and sunken upper eyelid in 9 patients improved significantly. Although orbital swelling occurred in the early postoperative period, no vision loss, eye movement limitation, or fat embolism had occurred. Autologous fat graft is an effective, predictable, scarless, and minimally invasive surgery for the correction of the sighted posttraumatic enophthalmos and sunken upper eyelid. The possible risk of fat embolization and blindness from the compression of the optic nerve should not be neglected. Further studies and more cases must be performed.


Follicle-stimulating hormone (FSH) regulates the expression of FSH receptor messenger ribonucleic acid in cultured Sertoli cells and in hypophysectomized rat testis.
FSH acts on Sertoli cells via interaction with a transmembrane receptor (FSHr). Control of expression of the receptor is surely a factor in the regulation of the action of FSH. The regulation of FSHr by FSH and testosterone was studied both in culture and in vivo. Sertoli cells from 18- to 20-day-old male rats were cultured in the presence of 25 ng/ml ovine (o) FSH. At 8 h after addition of FSH, expression of FSHr mRNA decreased significantly. Addition of FSH and actinomycin D to cells did not result in a further decrease in FSHr mRNA levels, suggesting that FSH does not alter turnover of FSHr mRNA. Treatment of cells with 40 ng/ml testosterone did not have any significant effect on the expression of FSHr mRNA. Hypophysectomy of 20-day-old male rats resulted in an increase in expression of FSHr mRNA as compared to that in sham-hypophysectomized animals. This increase was measured at 24 h posthypophysectomy and was maintained at 72 h after surgery. Injection of rats with 0.2 U oFSH at 48 h posthypophysectomy resulted in a reduction in FSHr mRNA when compared to the levels in hypophysectomized rats. Treatment with 2 mg testosterone propionate had no effect on FSHr mRNA levels. The findings confirm that FSH plays an important role in regulating mRNA expression of the FSHr in Sertoli cells in culture and show for the first time that FSHr mRNA is regulated in vivo by FSH in the immature rat testis.


UPLC-Q-TOF/MS-Based Metabolic Profiling Comparison of Two Major Bioactive Components and Their Metabolites in Normal and CKD Rat Plasma, Urine and Feces Following Oral Administration of Fructus Corni Extract.
Fructus Corni has been used for nourishing liver and kidney in clinical practice for many years. However, the in vivo integrated metabolism profile of its bioactive components remains unknown. In the present study, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry coupled with the MetaboLynxTM software was established for screening and identification of the metabolites of the loganin and the morroniside in normal and chronic kidney disease (CKD) rat plasma, urine and feces after oral administration of Fructus Corni extract. The results showed that 11 metabolites including taurine and glucuronide conjugates, deglycosylated, dehydrated, (de)hydroxylated, (de)methylated, acetylated products were tentatively detected in normal rat samples while only eight metabolites were obtained in the model samples. Two parent compounds were both absorbed into the blood circulation of the normal and CKD rats. However, the compounds in the CKD rat showed lower metabolic capability. Few kinds and minor amounts of the metabolites were appeared in the CKD rat plasma, urine and feces. While considerable amounts of the parent compounds were detected in the CKD plasma. This helped maintain a high blood drug concentration which might be beneficial for the treatment of CKD. These results will be helpful for the further investigation of the pharmacokinetic study of Fructus Corni in vivo.


The initial inositol 1,4,5-trisphosphate response induced by histamine is strongly amplified by Ca(2+) release from internal stores in smooth muscle.
We have studied the Ca(2+)-dependence and wortmannin-sensitivity of the initial inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) response induced by activation of either histamine or muscarinic receptors in smooth muscle from guinea pig urinary bladder. Activation of H(1) receptors with histamine (100 microM) produced a significant elevation in Ins(1,4,5)P(3) levels with only 5s stimulation and in the presence of external Ca(2+). However, this response was abolished fully by either the prolonged absence of external Ca(2+) or the depletion of internal Ca(2+) stores with thapsigargin (100nM) or ryanodine (10 microM). In contrast, the same conditions only slightly reduced the initial Ins(1,4,5)P(3) response induced by carbachol. The prolonged incubation of smooth muscle in 10 microM wortmannin to inhibit type III PI 4-kinase abolished both the early histamine-evoked Ins(1,4,5)P(3) and Ca(2+) responses. Conversely, wortmannin did not alter Ca(2+) release induced by carbachol, despite a partial reduction of its Ins(1,4,5)P(3) response. Collectively, these data indicate that the detectable histamine-induced increase in Ins(1,4,5)P(3) is more the consequence of Ca(2+) release from internal stores than a direct activation of phospholipase C by H(1) receptors. In addition, the effect of wortmannin implies the existence of a Ca(2+)-dependent amplification loop for the histamine-induced Ins(1,4,5)P(3) response in smooth muscle.


Effect of CeH2.73-CeO2 Composites on the Desorption Properties of Mg2NiH4.
A series of CeH2.73/CeO2 composites with different ratios of hydride and oxide phases are prepared from the pure cerium hydride via oxidation treatments in the air at room temperature, and they are subsequently doped into Mg2NiH4 by ball milling. The desorption properties of the as-prepared Mg2NiH4+CeH2.73/CeO2 composites are studied by thermogravimetry and differential scanning calorimetery. Microstructures are studied by scanning electron microscopy and transmission electron microscopy, and the phase transitions during dehydrogenation are analyzed through in situ X-ray diffraction. Results show that the initial dehydrogenation temperature and activation energy of Mg2NiH4 are maximally reduced by doping the CeH2.73/CeO2 composite with the same molar ratio of cerium hydride and oxide. In this case, the CeH2.73/CeO2 composite has the largest density of interface among them, and the hydrogen release effect at the interface between cerium hydride and oxide plays an efficient catalytic role in enhancing the hydrogen desorption properties of Mg2NiH4.


Coincidence Detection within the Excitable Rat Olfactory Bulb Granule Cell Spines.
In the mammalian olfactory bulb, the inhibitory axonless granule cells (GCs) feature reciprocal synapses that interconnect them with the principal neurons of the bulb, mitral, and tufted cells. These synapses are located within large excitable spines that can generate local action potentials (APs) upon synaptic input ("spine spike"). Moreover, GCs can fire global APs that propagate throughout the dendrite. Strikingly, local postsynaptic Ca2+ entry summates mostly linearly with Ca2+ entry due to coincident global APs generated by glomerular stimulation, although some underlying conductances should be inactivated. We investigated this phenomenon by constructing a compartmental GC model to simulate the pairing of local and global signals as a function of their temporal separation Δt. These simulations yield strongly sublinear summation of spine Ca2+ entry for the case of perfect coincidence Δt = 0 ms. Summation efficiency (SE) sharply rises for both positive and negative Δt. The SE reduction for coincident signals depends on the presence of voltage-gated Na+ channels in the spine head, while NMDARs are not essential. We experimentally validated the simulated SE in slices of juvenile rat brain (both sexes) by pairing two-photon uncaging of glutamate at spines and APs evoked by somatic current injection at various intervals Δt while imaging spine Ca2+ signals. Finally, the latencies of synaptically evoked global APs and EPSPs were found to correspond to Δt ≈ 10 ms, explaining the observed approximately linear summation of synaptic local and global signals. Our results provide additional evidence for the existence of the GC spine spike.SIGNIFICANCE STATEMENT Here we investigate the interaction of local synaptic inputs and global activation of a neuron by a backpropagating action potential within a dendritic spine with respect to local Ca2+ signaling. Our system of interest, the reciprocal spine of the olfactory bulb granule cell, is known to feature a special processing mode, namely, a synaptically triggered action potential that is restricted to the spine head. Therefore, coincidence detection of local and global signals follows different rules than in more conventional synapses. We unravel these rules using both simulations and experiments and find that signals coincident within ≈±7 ms around 0 ms result in sublinear summation of Ca2+ entry because of synaptic activation of voltage-gated Na+ channels within the spine.


[Diagnostic algorithms in female urinary incontinence].
Urinary incontinence is frequent problem with significantly negative impact on the quality of life. The correct plan of examination leads to the proposal of the appropriate treatment. The history, correct judgment of symptoms of incontinence and detailed gynaecological examination are important at the beginning of the diagnostic process. Negative urine cultivation is necessary condition for the invasive investigation of the urinary tract. Special questionnaires, micturition diary and clinical tests belong to the physical examination. The pad-weight test is based on the measurement of weight gain of absorbent pads during a test period under standardised conditions. Q-tip test (cotton swab test) measures the degree of mobility of urethra and bladder neck. Most of the clinical tests can be replaced by the ultrasound examination (introital or perineal approach), which helps to appreciate the vigour of urethra, bladder neck and vagina during the resting period and at stress. Urodynamic examination records pressure changes during the bladder filling, pressure gradients in urethra and the velocity of the urinary flow. It should be carried out when antiincontinence surgery is planned or when conservative therapy failed. Urodynamic examination helps to distinguish between stress and urge type of incontinence. Urethrocystoscopy is indicated for the diagnosis of the recurrent urinary infections, urge incontinence when structural pathologies of the urinary bladder are suspected, iatrogenic incontinence or postoperative complications.


Employment over the life course and post-retirement social networks: a gendered perspective.
The present study examines how different lifelong employment patterns are related to social relationships in old age, and whether there are gender differences in the impact of lifelong employment patterns. The study was based on data collected among European adults as part of the Health, Aging and Retirement Survey in Europe (SHARE) and focuses on retired adults. The study combines data on social relationships, collected in 2015, with retrospective data on employment history (number of jobs and years of employment) collected in 2017. The findings show that adults who worked in more jobs had overall better structural characteristics of their later life networks - they had larger social networks and were more likely to include children and friends within those networks but less likely to include their spouse. On the other hand, working in more jobs was related to less emotional closeness with the network. These results varied between men and women; women who were involved in the labor market over their life had larger social networks and tended to include friends as confidants. Among men, working for more years was related to higher emotional closeness with the social network. The study may indicate a gendered pattern of social advantages and disadvantages to involvement in the labor market over the work course. Practitioners should consider the lifelong employment of adults to identify those who might be at risk of social isolation.


Applications of Coarse-Grained Models in Metabolic Engineering.
Mathematical modeling is a promising tool for better understanding of cellular processes. In recent years, the development of coarse-grained models has gained attraction since these simple models are able to capture and describe a broad range of growth conditions. Coarse-grained models often comprise only two cellular components, a low molecular component as representative for central metabolism and energy generation and a macromolecular component, representing the entire proteome. A framework is presented that presents a strict mass conservative model for bacterial growth during a biotechnological production process. After providing interesting properties for the steady-state solution, applications are presented 1) for a production process of an amino acid and 2) production of a metabolite from central metabolism.


Orthogonal cell-based biosensing: fluorescent, electrochemical, and colorimetric detection with silica-immobilized cellular communities integrated with an ITO-glass/plastic laminate cartridge.
This is the first report of a living cell-based environmental sensing device capable of generating orthogonal fluorescent, electrochemical, and colorimetric signals in response to a single target analyte in complex media. Orthogonality is enabled by use of cellular communities that are engineered to provide distinct signals in response to the model analyte. Coupling these three signal transduction methods provides additional and/or complementary data regarding the sample which may reduce the impact of interferants and increase confidence in the sensor's output. Long-term stability of the cells was addressed via 3D entrapment within a nanostructured matrix derived from glycerated silicate, which allows the device to be sealed and stored under dry, ambient conditions for months with significant retention in cellular activity and viability (40% viability after 60 days). Furthermore, the first co-entrapment of eukaryotic and bacterial cells in a silica matrix is reported, demonstrating multianalyte biodetection by mixing disparate cell lines at intimate proximities which remain viable and responsive. These advances in cell-based biosensing open intriguing opportunities for integrating living cells with nanomaterials and macroscale systems.


Modeling the effect of operator and passenger characteristics on the fatality risk of motorcycle crashes.
In Iran more than 25% of crash fatalities belong to motorcycle operators and passengers in the recent years, from which about 20% are related to passenger fatalities. The aim of this study was to investigate the motorcycle operator and passenger characteristics as well as other contributory factors that may affect the fatality risk of motorcyclists involved in traffic crashes. To this end, motorcycle crash data between 2009 and 2012 was extracted from Iran traffic crash database and a logistic regression analysis was performed to obtain odds ratio estimates for each of the study variables. The fatality risk of motorcyclists has a direct relationship with the number of pillion passengers carried. Results also indicate that the amount of increase in the likelihood of having a fatality in a motorcycles crash is considerably higher when the operator is accompanied by a male passenger of the same age. Furthermore, results showed that if the crash is occurred in the darkness, on curves, in rural areas and on highways, then the crash would be more likely to be fatal. Moreover, the head-on collisions, older operators, unlicensed operators and not using a safety helmet were found to increase the likelihood of a fatality in a motorcycle crash. Preventative measures such as, imposing stricter rules regarding safety helmet usage and confining the number of pillion passengers to one, might be implemented to reduce the fatality risk in motorcycle crashes. In addition, more appropriate infrastructures for penalizing offending motorcyclists could also reduce the frequency of law violations such as not wearing helmet or riding without motorcycle license, which in turn, would result into a reduction in the fatality risk of motorcycle crashes.


[Selected prognostic factors of malignant uveal melanoma].
Malignant uveal melanoma is the most common intraocular tumor in adults. Despite very good local treatment results, patients' survival has not improved in the last decades. The main cause of death is metastatic spread, which occurs with a variable time delay after tumor discovery in 50% of patients. After metastasis development the mean survival rate decreases to less than 6 months. Progression to metastatic disease is associated with different prognostic factors. The spectrum of conventional clinical and histopathologic prognostic factors like age, tumor size, location, extrascleral growth, histopathologic cell type, vascularisation, invasion of sclera, etc., has been enlarged by using new immunological, molecular, immunohistochemical and cytogenetical methods. Current research also focuses on development of an adjuvant systemic therapy which could delay or prevent metastasis development in high-risk patients. It is necessary to determine reliable prognostic factors in order to select potential candidates for such a systemic treatment. In this article we present a short overview of known prognostic factors of uveal melanoma.