Group separation of peptides by ligand-exchange chromatography with a Sephadex containing N-(2-pyridylmethyl)glycine.
The synthesis of 2-hydroxy-3[N-(2-pyridylmethyl)glycine]propyl Sephadex ether--a new chelating resin--is described. This resin has been employed in the form of its Cu2+ complex to separate peptides, as a group, from alpha-amino acids and NaCl. Ninety-seven ligands of different structures were separated chromatographically at room temperature. It was shown that two structural parameters of the ligands control the separation process, namely, the presence of ligand donor groups and the possibility for them to form chelate rings of suitable size. Separation of peptides from alpha-, gamma-, delta-amino acids, N-acetyl derivatives of amino acids (except N-Ac-Trp), and NaCl is possible if the peptides fulfill the following structural requirements: the peptide molecule must have a free terminal amino group; a carbonyl group (of the peptide linkage) must be situated in the alpha- or beta-position of the free amino group; and the peptide may not contain an imidazole residue (except Gly-Gly-His). A relationship was found between the log k' and the corresponding pKHHL, log KCuCuL, and log KCuBipyCuBipyL values. Interpretation of the different K' values was possible based on the different basicities of the terminal amino groups and on the structures of the different side chains of the peptides.


Interactions between males guppies facilitates the transmission of the monogenean ectoparasite Gyrodactylus turnbulli.
In a previous study we found that female guppies shoaled more than males and that there was greater transmission of the ectoparasite Gyrodactylus turnbulli between females. Here, to test for a possible sex bias in parasite transmission, we conducted a similar experiment on single sex shoals of male and female guppies, observing host behaviour before and after the introduction of an infected shoal mate. The initial parasite burden was considerably lower in the present experiment (30 worms versus >100 worms previously) and we used a different stock of ornamental guppies (Green Cobra variety versus a Tuxedo hybrid previously). Contrary to our previous finding, males aggregated significantly more than females. Males performed 'sigmoid' displays towards each other, a courtship behaviour that is more generally directed towards females. Due to the high rate of male-male interactions, parasite transmission was 10 times higher between males than between females. Furthermore, shoaling intensity was highest for the most parasitised fish indicating that these infected fish were not avoided by non-parasitised conspecifics. These studies show that certain social behaviours including shoaling and courtship displays, appear to facilitate the transmission of gyrodactylid parasites.


Multislice method based full-space analysis on mechanical interaction of electron vortex beam with a crystalline particle.
A full-space analysis based on the multislice method is presented and has been applied to the simulation of mechanical interaction of electron vortex beam with a nanoparticle. The moment acting on the particle is calculated and presented as a moment map. We have calculated the total torque and compared it with the result from orbital angular momentum analysis. The thickness dependent torque and angular momentum are derived and discussed for different incident energies, convergence angles and angular momenta of the incident electron vortex beam. For different incident beams, the enhanced torque caused by diffraction enhancement is discussed. The oscillation behavior of the torque and angular momentum on depth is explained by a channeling theory. A comparison of thickness dependent angular momentum between the proposed analysis and conventional orbital angular momentum analysis in both the multislice method and the Bloch wave method is presented and discussed.


Chitosan chemistry review for living organisms encapsulation.
Microencapsulation is an emerging process in which an active substance is entrapped in a homogeneous or heterogeneous matrix to form capsules. This technique allows reducing the adverse effects of the external environment on encapsulated compounds, ensuring their stability through manipulation and transport besides enabling their controlled release. Microencapsulation is particularly suitable to protect sensitive materials such as living organisms, thus providing them an appropriate environment to behave and act as if they were in their natural habitat. The used matrix is generally composed of polymers, due to their ability to form flexible networks. Chitosan, a linear polysaccharide obtained from chitin, is a prime microencapsulation polymer by itself or in combination with other polymers owing to its cationic nature, biodegradability, non-toxicity and mucoadhesive properties. This review aims to present the diverse chitosan modifications, adaptations and crosslinking through the microencapsulation of somatic cells, bacteria, yeasts and microalgaes.


Pharmacokinetics of lomefloxacin in patients with cirrhosis.
The effect of liver failure on the pharmacokinetics of lomefloxacin was studied in 12 patients with cirrhosis. Patients received a single oral dose of 400 mg lomefloxacin, and blood and urine samples were collected at intervals over the next 48 hours. The concentrations of lomefloxacin in all samples were measured using high-pressure liquid chromatography (HPLC). The mean (+/- standard deviation) maximum plasma concentration (Cmax) in these patients was 3.9 +/- 1.20 micrograms/mL. The mean time to maximum serum concentration (Tmax) was 2.1 +/- 2.6 hours, and the mean elimination half-life (t1/2) was 9.16 +/- 1.93 hours. Mean renal clearance was 88.9 +/- 38.0 mL/min/1.73 m2, and the mean nonrenal clearance was 61.6 +/- 19.0 mL/min/1.73 m2, which corresponded to 41% of the total body clearance. No correlations were observed between nonrenal clearance and hepatic insufficiency (Pugh score) or nonrenal clearance and plasma bilirubin. These results show that liver failure does not per se affect lomefloxacin kinetics. Thus, no adjustments in lomefloxacin dosages appear to be necessary for patients with impaired liver function tests.


Diabetic oxidative stress-induced telomere damage aggravates periodontal bone loss in periodontitis.
Periodontitis, one of the most common oral complications of diabetes mellitus (DM), causes a reduction in alveolar bone height and loss of alveolar bone mass. It has been shown that DM aggravates the progression of periodontitis, but the mechanism remains inconclusive. The hyperglycemic environment of DM has been proven to generate reactive oxygen species (ROS). Since telomeres, guanine-rich repeats, are highly susceptible to oxidative attack, we speculate that the excessive accumulation of ROS in DM could induce telomere damage resulting in dysfunction of periodontal ligament cells, especially periodontal ligament stem cells (PDLSCs), which reduces the ability of tissue repair and reconstruction in diabetic periodontitis. In this study, our current data revealed that oxidative telomere damage occurred in the periodontal ligaments of diabetic mice. And Micro-CT scans showed reduced alveolar bone height and impaired alveolar bone mass in a diabetic periodontitis model. Next, cultured mouse PDLSCs (mPDLSCs) were treated with the oxidant tert-butyl hydroperoxide (t-BHP) in vitro, as we expected telomere damage was observed and resulted in cellular senescence and dysfunction. Taken together, oxidative stress in DM causes telomere dysfunction and PDLSCs senescence, which influences periodontal bone tissue regeneration and reconstruction and ultimately exacerbates bone loss in periodontitis.


The association between labor companionship and obstetric violence during childbirth in health facilities in five facilities in the occupied Palestinian territory.
Studies show that the presence of companionship during childbirth leads to positive outcomes for women. This study investigates the protective effect of having a labor companion on obstetric violence in the health facilities of the Occupied Palestinian Territory. A secondary analysis of a cross-sectional study of women who gave birth in five health centers in the occupied Palestinian territory up to 8 weeks following childbirth was performed. The presence of a labor companion was examined in relation to socioeconomic variables and physical abuse, verbal abuse or stigma or discrimination, failure to achieve professional standards, vaginal examinations, and pain relief. According to the findings, the total number of women with a labor partner or a birth companion present at any stage during the labor process was 92% in the West Bank, and 77.4% in the Gaza Strip. According to the timing of support, 23.5% of women had a labor companion present during labor, childbirth, and after childbirth whilst in the hospital. Women who did not have labor companions were more likely than women who did to report at least one sort of mistreatment, such as unconsented procedures. Women with a labor companion were less likely to report abuse (16%) compared to women without labor companion. In terms of informed permission for procedures, 75% of women who did not have a labor companion had unconsented episiotomy. Labor companionship assists women by providing them with companions who are less likely to be mistreated during labor. Efforts should be made to best implement the presence of labor companions, including the duration of the labor companionship and women's preferences.


Alleviation of maternal hyperthermia-induced early embryonic death by administration of melatonin to mice.
Maternal hyperthermia induces early embryonic death via increased oxidative stress to the embryo. In this study, we examined whether melatonin administered to heat-stressed pregnant mice would reduce hyperthermia-induced embryonic death. Mice were heat stressed (12 hr at 35 degrees C, 60% relative humidity) on the day of mating and melatonin (3 mg/kg body weight) was injected subcutaneously every 2 hr during heat exposure. Thereafter, zygotes were collected, and in vitro developmental ability and intracellular glutathione (GSH) content were assessed. In addition, reactive oxygen species (ROS) levels and free radical scavenging activity (FRSA) in the oviduct as well as lipid peroxidation in the liver were measured. Melatonin administration was associated with a tendency for higher intracellular GSH content in zygotes (1.67 pmol/zygote) and a significantly higher percentage of embryos that developed to the morula or blastocyst stage (47.91%; P < 0.01) compared with the parameters in heat-stressed mice that were administered a placebo (1.48 pmol GSH/zygote and 14.78% development). Lipid peroxidation levels in the liver and ROS levels in the oviduct were the same in melatonin-treated stressed mice and the controls, while these parameters were significantly higher in heat-stressed mice that were not treated with melatonin. Furthermore, FRSA in the oviduct was significantly (P < 0.05) higher in the melatonin-treated mice than in the controls. These results suggest that administration of melatonin to heat-stressed mice alleviates hyperthermia-induced early embryonic death and that this is accomplished in part by maintaining a neutral redox status within the mother.


Massively parallel sequencing for early molecular diagnosis in Leber congenital amaurosis.
Leber congenital amaurosis (LCA) is a rare congenital retinal dystrophy associated with 16 genes. Recent breakthroughs in LCA gene therapy offer the first prospect of treating inherited blindness, which requires an unequivocal and early molecular diagnosis. While present genetic tests do not address this due to a tremendous genetic heterogeneity, massively parallel sequencing (MPS) strategies might bring a solution. Here, we developed a comprehensive molecular test for LCA based on targeted MPS of all exons of 16 known LCA genes. We designed a unique and flexible workflow for targeted resequencing of all 236 exons from 16 LCA genes based on quantitative PCR (qPCR) amplicon ligation, shearing, and parallel sequencing of multiple patients on a single lane of a short-read sequencer. Twenty-two prescreened LCA patients were included, five of whom had a known molecular cause. Validation of 107 variations was performed as proof of concept. In addition, the causal genetic defect and a single heterozygous mutation were identified in 3 and 5, respectively, of 17 patients without previously identified mutations. We propose a novel targeted MPS-based approach that is suitable for accurate, fast, and cost-effective early molecular testing in LCA, and easily applicable in other genetic disorders.


Psychosocial impacts of the COVID-19 pandemic from a cross-sectional Survey of people living with HIV in Washington, DC.
COVID-19 has not only taken a staggering toll in terms of cases and lives lost, but also in its psychosocial effects. We assessed the psychosocial impacts of the COVID-19 pandemic in a large cohort of people with HIV (PWH) in Washington DC and evaluated the association of various demographic and clinical characteristics with psychosocial impacts. From October 2020 to December 2021, DC Cohort participants were invited to complete a survey capturing psychosocial outcomes influenced by the COVID-19 pandemic. Some demographic variables were also collected in the survey, and survey results were matched to additional demographic data and laboratory data from the DC Cohort database. Data analyses included descriptive statistics and multivariable logistic regression models to evaluate the association between demographic and clinical characteristics and psychosocial impacts, assessed individually and in overarching categories (financial/employment, mental health, decreased social connection, and substance use). Of 891 participants, the median age was 46 years old, 65% were male, and 76% were of non-Hispanic Black race/ethnicity. The most commonly reported psychosocial impact categories were mental health (78% of sample) and financial/employment (56% of sample). In our sample, older age was protective against all adverse psychosocial impacts. Additionally, those who were more educated reported fewer financial impacts but more mental health impacts, decreased social connection, and increased substance use. Males reported increased substance use compared with females. The COVID-19 pandemic has had substantial psychosocial impacts on PWH, and resiliency may have helped shield older adults from some of these effects. As the pandemic continues, measures to aid groups vulnerable to these psychosocial impacts are critical to help ensure continued success towards healthy living with HIV.


Epistaxis: medical versus surgical therapy: a comparison of efficacy, complications, and economic considerations.
A retrospective review of 4 years experience with over 32 epistaxis patients requiring hospitalization and using a standard medical or surgical therapy for control is presented. Medical therapy included the use of anterior nasal packing alone or in association with intranasal and nasopharyngeal balloon tamponade. Surgical therapy, for the most part, consisted of ethmoid and/or internal maxillary artery ligations. Most patients were treated initially with packing and balloons. Fifty-two percent of the group failed this therapy and required ligations for control. The patients who did not come to operation had fewer complications, a shorter average hospital stay, and lower average cost of hospitalization without increased risk of future epistaxis. An analysis is made comparing the results, complications, and financial implications of these two approaches.


[The presence of a thermally stable domain in the spiral part of a collagen molecule].
It is shown that in 0,5 M NaCl 8 M CH3COOH heat absorption and the second structure alteration in a heated solution proceed between two stages following one another, and besides, salts not only decrease the macromolecule denaturation temperature in total, but produce different destabilization effect on different regions. The presence of the thermostable domain in the macromolecule helical part permits investigation of the folding mechanism of the triple collagen helix under partial denaturation. The localization and biological role of the stable domain in the triple helix formation are suggested.


Morphine induces late cardioprotection in rat hearts in vivo: the involvement of opioid receptors and nuclear transcription factor kappaB.
Delta1-opioid receptor agonists can induce cardioprotection by early and late preconditioning (LPC). Morphine (MO) is commonly used for pain treatment during acute coronary syndromes. We investigated whether MO can induce myocardial protection by LPC and whether a nuclear transcription factor kappaB (NF-kappaB)-dependent intracellular signaling pathway is involved. Rats were subjected to 25 min of regional ischemia and 2 h of reperfusion 24 h after treatment with saline (NaCl; 0.9% 5 mL), lipopolysaccharide of Escherichia coli (LPS; 1 mg/kg), or MO (3 mg/kg). LPS is a trigger of LPC and served as positive control. Naloxone (NAL) was used to investigate the role of opioid receptors in LPC and was given before NaCl, LPS, or MO application (trigger phase) or before ischemia-reperfusion (mediator phase). Infarct size (percentage area at risk) was 59% +/- 9%, 51% +/- 6%, or 53% +/- 10% in the NaCl, NAL-NaCl, and NaCl-NAL groups, respectively. Pretreatment with MO reduced infarct size to 20% +/- 6% after 24 h (MO-24h), and this effect was abolished by NAL in the trigger (NAL-MO, 53% +/- 14%) and in the mediator (MO-NAL, 60% +/- 8%) phases. Pretreatment with LPS reduced infarct size to 23% +/- 8%. NAL administration in the trigger phase had no effect on infarct size (NAL-LPS 30% +/- 16%), whereas NAL during the mediator phase of LPC abolished the LPS-induced cardioprotection (LPS-NAL 54% +/- 8%). The role of NF-kappaB in morphine-induced LPC was investigated by Western blot and electrophoretic mobility shift assay. Morphine and LPS treatment increased phosphorylation of the inhibitory protein kappaB, leading to an increased activity of NF-kappaB. Thus, MO induces LPC similarly to LPS and it is likely that this cardioprotection is mediated at least in part by activation of NF-kappaB. Opioid receptors are involved as mediators in both MO- and LPS-induced LPC but as triggers only in MO-induced LPC. Like lipopolysaccharide, morphine induces late preconditioning and activation of nuclear transcription factor-kappaB. Opioid receptors are involved as mediators in both morphine- and lipopolysaccharide-induced late preconditioning but as triggers only in morphine-induced late preconditioning.


[Role of the caudate nucleus in the development of evoked synchronized activity].
Evoked spindles, recruitment and augmention to thalamic stimulation were studied in chronic cats after lesions of the caudate nuclei. The duration of spindles in the frontal cortex, thalamic and striatal sites were reduced to 3-4 oscillations. Their amplitude significantly decreased up to 50-10% in the thalamic and striatal sites. In the frontal cortex this decrease was not constant and sometimes was insignificant. Unilateral lesion of the caudate nucleus suppressed the synchronous activity evoked only by the ipsilateral thalamic stimulation. Lesion of the striatum (n. caudatus, globus pallidum, n. entopeduncularis, putamen) did not abolish the synchronous activity. It is suggested that the caudate nucleus produces ipsilateral facilitatory effect on the nonspecific thalamic system during the evoked synchronous activity.


Eukaryotic mRNAs encoding abundant and scarce proteins are statistically dissimilar in many structural features.
It is well known that non-coding mRNA sequences are dissimilar in many structural features. For individual mRNAs correlations were found for some of these features and their translational efficiency. However, no systematic statistical analysis was undertaken to relate protein abundance and structural characteristics of mRNA encoding the given protein. We have demonstrated that structural and contextual features of eukaryotic mRNAs encoding high- and low-abundant proteins differ in the 5' untranslated regions (UTR). Statistically, 5' UTRs of low-expression mRNAs are longer, their guanine plus cytosine content is higher, they have a less optimal context of the translation initiation codons of the main open reading frames and contain more frequently upstream AUG than 5' UTRs of high-expression mRNAs. Apart from the differences in 5' UTRs, high-expression mRNAs contain stronger termination signals. Structural features of low- and high-expression mRNAs are likely to contribute to the yield of their protein products.


Effects of protein-free diet in amino acid homeostasis of rat blood plasma and gut contents.
Amino acids in rat systemic and portal vein plasma and jejunal and ileal gut contents after 7 days of feeding normoprotein (NP) and protein-free diet (PF) are investigated. Amino acid analyses revealed that ingestion of PF diet resulted in unusual amino acid patterns in both plasmas. Thus, while the levels and/or molar ratios of all indispensable amino acids were significantly decreased, those of several gluconeogenetic amino acids, especially of glycine and alanine, were increased in both plasmas, but particularly in portal. By contrast, the molar ratios of the majority of amino acids in jejunal and ileal contents were not changed by PF diet.


Mixed-type primary germ cell tumor of the mediastinum in a young adult male with a sudden life threatening condition: A case report.
Primary germ cell tumors of the mediastinum are rare neoplasms. Above all, choriocarcinomas are highly aggressive with early haematogenous dissemination. Here, we report an extremely rare case of mixed-type primary germ cell tumor of the mediastinum which occurred in a 26-year-old man with multiple metastases of the lung caused by choriocarcinoma components, with diffuse pulmonary hemorrhaging. The patient developed a sudden life threatening condition a few days after a needle biopsy. KEY POINTS: Significant findings of the study: This was an extremely rare case of mixed-type germ cell tumor in a young adult male who developed a sudden life threatening condition due to choriocarcinoma components just a few days after a needle biopsy. What this study adds: Serious conditions may occur in patients with germ cell tumor containing choriocarcinoma components. At present, there is no other way to treat such patients than to promptly recognize complications and perform urgent multimodal intervention.


Long-term metformin treatment in adolescents with obesity and insulin resistance, results of an open label extension study.
Off-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin treatment in adolescents with obesity are scarce. Therefore, an 18 month open label extension study following an 18 months randomized placebo-controlled trial (RCT) on the efficacy, safety, and tolerability of metformin in adolescents with obesity and insulin resistance was performed. After completion of the RCT, metformin was offered to all participants with a body mass index standard deviation score (BMI-sds) > 2.3 and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) ≥ 3.4. Endpoints were change in BMI and HOMA-IR. Overall, 31/42 participants completed the extension study (74% girls, median age 14.8 (11.6 - 17.9), BMI 31.2 (22.3 - 45.1), HOMA-IR 3.4 (0.2 - 8.8)). At start, 22/42 (52.4%) participants were eligible for metformin of which 13 (59.0%) agreed with treatment. In participants who continued metformin, an increase was observed in BMI (+2.2 (+0.2 to +9.0)) and HOMA-IR (+13.7 (+1.6 to +48.3)). In metformin naive participants, BMI stabilized after an initial decrease (+0.5 (-2.1 to +5.1)). For HOMA-IR, a decrease was observed (-1.1 (-4.6 to +1.4)). While metformin treatment in metformin naive participants seems to result in an initial decrease in BMI and HOMA-IR, there is no evidence for sustained effect after prolonged use in adolescents. Limited compliance and/or insufficient dose may explain the differences in long-term effects between adolescents and adults.


Gene transfection with human hepatocyte growth factor complementary DNA plasmids attenuates cardiac remodeling after acute myocardial infarction in goat hearts implanted with ventricular assist devices.
Although a left ventricular assist device is often used to provide circulatory support until transplantation in severe heart failure, the mortality of long-term use of left ventricular assist devices remains high. We have shown that hepatocyte growth factor causes angiogenesis, antifibrosis, and antiapoptosis in the myocardium. Therefore, gene therapy with hepatocyte growth factor-complementary DNA plasmids may enhance the chance of "bridge to recovery." In this study, we performed gene therapy with hepatocyte growth factor in the impaired goat heart with a left ventricular assist device. Cardiac impairment was induced in 6 adult goats (56-65 kg) by ligation of the coronary artery, and ventricular assist devices were installed. The hepatocyte growth factor group (HGF; n = 3) was administered human hepatocyte growth factor-complementary DNA plasmid (2.0 mg) in the myocardium. The control group (n = 3) was similarly administered beta-galactosidase plasmid. Four weeks after gene transfection, we attempted to wean all goats from the ventricular assist device. The myocardia transfected with human hepatocyte growth factor-complementary DNA contained human hepatocyte growth factor protein at levels as high as 1.0 +/- 0.3 ng/g tissue 3 days after transfection. After weaning from the ventricular assist device, the HGF group showed good hemodynamics, whereas the control group showed deterioration. The percentage of fractional shortening was significantly higher in the HGF group than the control group (HGF vs control, 37.9% +/- 1.7% vs 26.4% +/- 0.3%, respectively; P < .01). Left ventricular dilatation associated with myocyte hypertrophy and fibrotic changes was detected in the control group but not in the HGF group. Vascular density was markedly increased in the HGF group. These results suggest that gene therapy with human hepatocyte growth factor may enhance the chance of bridge to recovery in the impaired heart supported with a ventricular assist device.


Anti-alpha enolase multi-antibody specificity in human diseases. Clinical significance and molecular mechanisms.
Alpha-enolase (Eno) is an ubiquitary glycolytic enzyme playing multiple functions that go well beyond its principal metabolic role of energy supplier during glycolysis. Eno is localized in the cytoplasm, but also expressed on the cell membrane, where it binds plasminogen allowing its activation. Its shorter form, in the nucleus, acts as transcription factor. In inflammatory conditions, Eno undergoes post-translational modifications, such as citrullination, oxidation and phosphorylation. Eno is also an autoantigen in different disorders. In fact, autoantibodies to Eno have been detected in rheumatoid arthritis, lupus nephritis, primary glomerulonephritis, cancer, infections and other disorders, and in many cases they represent specific markers to be utilized in clinical practice. Anti-Eno antibodies in the different clinical conditions are not equal: they differ in isotype and often recognize different epitopes on the enzyme. IgG1 and IgG3 are prevalent in Rheumatoid Arthritis, IgG2 in Lupus nephritis and IgG4 in primary autoimmune glomerulopathy. This review analyzes the characteristics of anti-Eno autoantibodies in autoimmune disorders and cancer, describing their fine specificity and isotype restriction. The post-translational modifications that are target of autoantibodies are also discussed, as they represent the basis for elucidating the molecular mechanisms responsible for epitope generation. Despite an impressive amount of experimental work on anti-Eno antibodies, it is still necessary to validate the use of anti-Eno antibodies as biomarkers of selected diseases and extend the knowledge on the mechanisms of anti-Eno autoantibody production. Strategies that downmodulate the immune response to Eno may represent in the future novel approaches in the treatment of autoimmune disorders.


A nomogram for predicting the probability of carcinoma in patients with intraductal papillary-mucinous neoplasm.
The objective of the present study was to use clinical and laboratory data to develop a model for predicting the presence of carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN). Data were collected on 81 patients with IPMN who underwent a pancreatic resection between 1989 and 2008 at Aichi Cancer Center Hospital. Variables analyzed included age, gender, laboratory findings (serum amylase, carcinoembryonic antigen, and carbohydrate antigen 19-9 level), pancreatic juice cytology grade, and imaging studies. Factors associated with the presence of carcinoma were evaluated by univariate and multivariate logistic regression analysis. Among the 81 patients with IPMN, 34 (42%) had malignant tumors (noninvasive carcinoma in 22 and invasive carcinoma in 12), and 47 (58%) had adenoma. On multivariate analysis, existing carcinoma was associated with female gender, main pancreatic duct IPMN, nodule size, and pancreatic juice cytology grade. Based on these variables, a predictive nomogram was developed. The area under the receiver operating characteristic curve (AUC) for the model was 0.903. The sensitivity and specificity of the model were 97.1 and 68.1%, respectively, in the validation study, for which the predictive probability of >10% was used to indicate the presence of carcinoma. The nomogram has high diagnostic predictability for carcinoma in patients with IPMN and for individual cancer probability. This instrument may help to identify patients who need a surgical procedure.


Patient-reported outcomes of adults with congenital heart disease from eight European countries: scrutinising the association with healthcare system performance.
Inter-country variation in patient-reported outcomes of adults with congenital heart disease has been observed. Country-specific characteristics may play a role. A previous study found an association between healthcare system performance and patient-reported outcomes. However, it remains unknown which specific components of the countries' healthcare system performance are of importance for patient-reported outcomes. The aim of this study was to investigate the relationship between components of healthcare system performance and patient-reported outcomes in a large sample of adults with congenital heart disease. A total of 1591 adults with congenital heart disease (median age 34 years; 51% men; 32% simple, 48% moderate and 20% complex defects) from eight European countries were included in this cross-sectional study. The following patient-reported outcomes were measured: perceived physical and mental health, psychological distress, health behaviours and quality of life. The Euro Health Consumer Index 2015 and the Euro Heart Index 2016 were used as measures of healthcare system performance. General linear mixed models were conducted, adjusting for patient-specific variables and unmeasured country differences. Health risk behaviours were associated with the Euro Health Consumer Index subdomains about patient rights and information, health outcomes and financing and access to pharmaceuticals. Perceived physical health was associated with the Euro Health Consumer Index subdomain about prevention of chronic diseases. Subscales of the Euro Heart Index were not associated with patient-reported outcomes. Several features of healthcare system performance are associated with perceived physical health and health risk behaviour in adults with congenital heart disease. Before recommendations for policy-makers and clinicians can be conducted, future research ought to investigate the impact of the healthcare system performance on outcomes further.


4-Phenylureido/thioureido-substituted 2,2-dimethylchroman analogs of cromakalim bearing a bulky 'carbamate' moiety at the 6-position as potent inhibitors of glucose-sensitive insulin secretion.
The synthesis of 2,2-dimethylchromans bearing a 3/4-chloro/cyano-substituted phenylureido or phenylthioureido moiety at the 4-position and an alkoxycarbonylamino ('carbamate') group at the 6-position is described. These new analogs of the potassium channel opener (±)-cromakalim were further tested on rat pancreatic islets as putative inhibitors of insulin release and on rat aorta rings as putative vasorelaxants. All compounds inhibited insulin secretion and induced a myorelaxant activity. Compound 14o [R/S-N-3-cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)urea; BPDZ 711] emerged as the most potent inhibitor of the glucose-sensitive insulin releasing process (IC50 = 0.24 μM) and displayed selectivity towards the pancreatic endocrine tissue. Radioisotopic, fluorimetric and pharmacological investigations were performed on rat pancreatic islet and rat vascular smooth muscle cells in order to decipher its mechanism of action. Our findings suggest that the mechanism of action of 14o is rather unspecific. The compound behaves as a KATP channel opener, a Ca(2+) entry blocker, and promotes an intracellular calcium translocation.


Structures, energies and bonding in neutral and charged Li microclusters.
Structural and chemical properties of charged and neutral Lithium microclusters are investigated for [Formula: see text]. A total of 18 quantum conformational spaces are randomly walked to produce candidate structures for local minima. Very rich potential energy surfaces are produced, with the largest structural complexity predicted for anionic clusters. Analysis of the electron charge distributions using the quantum theory of atoms in molecules (QTAIM) predicts major stabilizing roles of Non-nuclear attractors (NNAs) via NNA···Li interactions with virtually no direct Li···Li interactions, except in the least stable configurations. A transition in behavior for clusters containing more than seven nuclei is observed by using the recently introduced quantum topology to determine in a quantum mechanically consistent fashion the number of spatial dimensions each cluster has. We experiment with a novel scheme for extracting persistent structural motifs with increase in cluster size. The new structural motifs correlate well with the energetic stability, particularly in highlighting the least stable structures. Quantifying the degree of covalent character in Lithium bonding independently agrees with the observation in the transition in cluster behavior for lithium clusters containing more than seven nuclei. Good correlation with available experimental data is obtained for all properties reported in this work.


Insights into the precipitation kinetics of CaCO3 particles in the presence of polystyrene sulfonate using in situ small-angle X-ray scattering.
The formation of calcium carbonate (CaCO3) nanoparticles (NPs) in the presence of polystyrene sulfonate (PSS) as an additive was examined by time-resolved small-angle X-ray scattering (SAXS) in a flow system that mimics experimental conditions used at home facilities where the precipitation can be achieved in a beaker. The experiments were carried out at low concentrations to remain in the dilute regime. A model-independent analysis was performed using the Porod invariant which defines the scale factor, leaving only the distribution of radii as the adjustable parameter. The presence of the PSS additive strongly retards the precipitation of CaCO3 NPs. The formation of NPs reaches a state of equilibrium after a few minutes. Here, it is shown that the concentration of precursors at a fixed PSS concentration plays a key role in determining the size of the NPs obtained. A full analysis of the SAXS patterns was carried out using the Hurd-Flower model to account for the weaker intensity decay than the classical Porod behaviour. The temporal evolution of the particle radii was determined. Wide-angle X-ray scattering experiments carried out simultaneously show that the particles formed have the structure of vaterite with growth consistent with the evolution of the Porod invariant.


Computational investigation of the haemodynamics shows criticalities of central venous lines used for chronic haemodialysis in children.
Haemodialysis is a life-saving treatment for children with kidney failure. The majority of children have haemodialysis through central venous lines (CVLs). The use of CVLs in pediatric patients is often associated to complications which can lead to their replacement. The aim of this study is to investigate haemodynamics of pediatric CVLs to highlight the criticalities of different line designs. Four models of CVLs for pediatric use were included in this study. The selected devices varied in terms of design and sizes (from 6.5 Fr to 14 Fr). Accurate 3D models of CVLs were reconstructed from high-resolution images including venous and arterial lumens, tips and side holes. Computational fluid dynamics (CFD) analyses were carried out to simulate pediatric working conditions of CVLs in ideal and anatomically relevant conditions. The arterial lumens of all tested CVLs showed the most critical conditions with the majority of blood flowing through the side-holes. A zone of low flow was identified at the lines' tip. The highest shear stresses distribution (>10 Pa) was found in the 8 Fr line while the highest platelet lysis index in the 10 Fr model. The analysis on the anatomical geometry showed an increase in wall shear stress measured in the 10 F model compared to the idealised configuration. Similarly, in anatomical models an increased disturbance and velocity of the flow was found inside the vein after line placement. This study provided a numerical characterization of fluid dynamics in pediatric CVLs highlighting performance criticalities (i.e. high shear stresses and areas of stagnation) associated to specific sizes (8 Fr and 10 Fr) and conditions (i.e. anatomical test).


Talus Bipartitus Etiology - Is Neonatal Infection Involved?
Talus bipartitus is a rare skeletal variation. Several causative factors have been proposed, but none of them seem to be convincing. We hypothesize that talus bipartitus may result from ossification disruption in neonatal period caused possibly by an infection. The observations supporting this link are discussed. The hypothesis is supported by two cases with symptomatic talus bipartitus illustrating the postulated connection. ankle, pain etiology, talus abnormalities, talus bipartitus.


Gastrointestinal symptoms and bowel patterns across the menstrual cycle in dysmenorrhea.
Gastrointestinal (GI) functional indicators and symptoms across the menstrual cycle were examined in three groups of women: dysmenorrheic (n = 15), non-pill-taking nondysmenorrheic (n = 10), and nondysmenorrheic taking birth control pills (BCPs) (n = 9). Group assignment was based on the reported presence or absence of moderate to severe menstrual cramps in a GI Health Diary which subjects kept for two menstrual cycles. Stool consistencies and frequencies and GI symptoms were also recorded in this diary. Menstrual cycle phase significantly, p = .03, influenced stool consistencies for the sample as a whole with the loosest stools at menses. Reports of stomach pain were higher, p less than .001, at menses than at other cycle phases in all groups, and nausea, p less than .001, and decreased food intake, p less than .01, were more frequently reported by dysmenorrheic women at menses. More dysmenorrheic women had a history of menses-related GI symptoms. Both cycle phase and group differences were significant, p less than .05, for menstrual distress, with negative affect, pain, behavior changes, and autonomic reactions reported more frequently at menses by dysmenorrheic women.


Recent progress and future prospects on halide perovskite nanocrystals for optoelectronics and beyond.
As an emerging new class of semiconductor nanomaterials, halide perovskite (ABX3, X = Cl, Br, or I) nanocrystals (NCs) are attracting increasing attention owing to their great potential in optoelectronics and beyond. This field has experienced rapid breakthroughs over the past few years. In this comprehensive review, halide perovskite NCs that are either freestanding or embedded in a matrix (e.g., perovskites, metal-organic frameworks, glass) will be discussed. We will summarize recent progress on the synthesis and post-synthesis methods of halide perovskite NCs. Characterizations of halide perovskite NCs by using a variety of techniques will be present. Tremendous efforts to tailor the optical and electronic properties of halide perovskite NCs in terms of manipulating their size, surface, and component will be highlighted. Physical insights gained on the unique optical and charge-carrier transport properties will be provided. Importantly, the growing potential of halide perovskite NCs for advancing optoelectronic applications and beyond including light-emitting devices (LEDs), solar cells, scintillators and X-ray imaging, lasers, thin-film transistors (TFTs), artificial synapses, and light communication will be extensively discussed, along with prospecting their development in the future.


Heterogeneous distribution of polysialylated neuronal-cell adhesion molecule during post-natal development and in the adult: an immunohistochemical study in the rat brain.
A monoclonal antibody raised against the capsular polysaccharides of meningococcus B was used for immunohistochemical studies in the rat brain, with particular focus on the substantia nigra. This antibody recognizes polysialic acid residues specifically associated with the neuronal-cell adhesion molecule, and reacts with the highly sialylated embryonic neuronal-cell adhesion molecule, but not with the weakly sialylated adult form of the molecule. Immunoreactivity to this monoclonal antibody was intense and widespread in the brain of 1-10-day-old hooded rats. Immunolabeling was associated with cell membranes and present in the intersomata space. In sections from 16- and 25-day-old rats, marked heterogeneity in the level of immunostaining appeared among individual brain nuclei. Areas devoid of labeling with the anti-meningococcus antibody still expressed immunoreactivity to a polyclonal anti-neuronal-cell adhesion molecule antibody. This suggests that the loss of immunostaining with the monoclonal antibody did not correspond to a loss of expression of neuronal-cell adhesion molecule, but to a maturation from the embryonic to the adult form of the molecule, occurring at different rates in various brain regions. In 2-month-old rats, immunolabeling with the monoclonal antibody was still present in discrete brain areas, including the substantia nigra, suggesting that the presence of highly sialylated neuronal-cell adhesion molecule outlasts post-natal development in those brain regions. It is proposed that neuronal-cell adhesion molecule associated polysialic residues may play a role in neuronal plasticity in restricted areas of the adult brain.


The in vivo erythrocyte micronucleus test: measurement at steady state increases assay efficiency and permits integration with toxicity studies.
The mouse erythrocyte micronucleus assay has been traditionally carried out using one or two exposures to the test agent, followed by sampling at two or three postexposure times to obtain a sample near the time of the transient peak of micronucleated polychromatic erythrocytes (PCEs). We have demonstrated that frequencies of micronucleated RNA-positive (PCEs) and RNA-negative erythrocytes in blood and bone marrow come to steady state during "continuous" exposure via diet or drinking water, or during repeated daily exposures to test agents by ip injection, gavage, or inhalation. Under these exposure conditions, frequencies of micronucleated cells in peripheral blood approached steady state within 2-3 days in RNA-positive erythrocytes and in 5-6 weeks in RNA-negative erythrocytes. With exposure durations of 6 days (monocrotaline or Crotalaria seeds in diet), 10 days (triethylenemelamine, mitomycin C, 7,12-dimethylbenzanthracene, or colchicine, ip daily), 90 days (triethylenemelamine or urethan in drinking water or 1,3-butadiene via inhalation), or 2 years (benezene by daily gavage), frequencies of micronucleated cells attained and remained at steady state for prolonged periods. At steady state, frequencies of micronucleated RNA-positive cells in bone marrow samples were similar to those in RNA-positive and RNA-negative cells in peripheral blood (e.g., triethylenemelamine in drinking water at 4 micrograms/ml resulted in frequencies of micronucleated RNA-negative erythrocytes in peripheral blood of 27/1000 after 45 days of exposure and 24/1000 after 90 days, with a frequency of 28/1000 in bone marrow RNA-positive erythrocytes after 90 days). The data suggest that the efficiency of the assay would be markedly improved by using a repeated dose schedule with a single sample taken at steady state, rather than scoring multiple samples at various times after a single dose. This approach allows the frequency of micronucleated cells to be measured in a sample of bone marrow or blood obtained at almost any stage of routine toxicity testing.


Usefulness and pitfall of Narrow band imaging combined with magnifying endoscopy for detecting an unknown head and neck primary site with cervical lymph node metastasis.
Cervical nodal metastasis from clinically undetectable primary squamous cell carcinoma (SCC) accounts for 1-2% of head and neck malignancies. We retrospectively evaluate the ability of Narrow band imaging combined with magnifying endoscopy (NBI-ME) to detect the primary sites of superficial SCC in the head and neck region. This was a report of 11 patients. We performed with NBI-ME to detect unknown primary sites in the head and neck. Among 11 patients, primary sites were detected in eight. Primary sites were detected in the head and neck in 6 (54.5%) of 11 patients on NBI-ME, all 6 primary lesions were a flat lesion. Two patients in whom primary lesions could not be detected on NBI-ME, one had submucosal tumor like lesion, the other featured by a detectable primary lesion 19 months after neck dissection. NBI-ME can be recommended as an essential procedure for the detection of primary lesions in patients with primary unknown cervical lymph node metastasis.


Genomic Predictions of Phenotypes and Pseudo-Phenotypes for Viral Nervous Necrosis Resistance, Cortisol Concentration, Antibody Titer and Body Weight in European Sea Bass.
In European sea bass (Dicentrarchus labrax L.), the viral nervous necrosis mortality (MORT), post-stress cortisol concentration (HC), antibody titer (AT) against nervous necrosis virus and body weight (BW) show significant heritability, which makes selective breeding a possible option for their improvement. An experimental population (N = 650) generated by a commercial broodstock was phenotyped for the aforementioned traits and genotyped with a genome-wide SNP panel (16,075 markers). We compared the predictive accuracies of three Bayesian models (Bayes B, Bayes C and Bayesian Ridge Regression) and a machine-learning method (Random Forest). The prediction accuracy of the EBV for MORT was approximately 0.90, whereas the prediction accuracies of the EBV and the phenotype were 0.86 and 0.21 for HC, 0.79 and 0.26 for AT and 0.71 and 0.38 for BW. The genomic prediction of the EBV for MORT used to classify the phenotype for the same trait showed moderate classification performance. Genome-wide association studies confirmed the polygenic nature of MORT and demonstrated a complex genetic structure for HC and AT. Genomic predictions of the EBV for MORT could potentially be used to classify the phenotype of the same trait, though further investigations on a larger experimental population are needed.


Abnormal anti-viral immune response in mice is corrected in HLA-B27.2-transgenic mice.
In contrast to the strong Sendai virus-specific cytotoxic T-lymphocyte (CTL) responses in C57BL/6 mice. H-2Kb mutant bm1 mice are nonresponders to Sendai virus. By appropriate crossings between HLA-B27 double-transgenic mice and Kb mutant bm1 mice, and after subsequent selection, H-2bm1 homozygous mice were produced expressing the human HLA-B27.2 and beta 2-microglobulin genes. Here we show that the introduction of a human HLA class I gene into the genome of the H-2bm1 Sendai virus-nonresponder mutant mice resulted in good responsiveness to Sendai virus, and in normal levels of Sendai virus-specific CTL precursors. The CTL response in the HLA-B27.2 double-transgenic H-2bm1 mice against Sendai virus was restricted by the HLA-B27.2 molecule. These results show the direct involvement of HLA class I molecules in regulation of the anti-viral CTL repertoire and represent for the first time a correction of abnormal anti-viral immunity in mice by incorporation of a human MHC class I (HLA-B27.2) gene.


Morin inhibited lung cancer cells viability, growth, and migration by suppressing miR-135b and inducing its target CCNG2.
Lung cancer is one of the most severe threats with the highest mortality rate to humans in the world. Recently, morin has been reported to have anti-tumor properties observed in several types of cancers. However, its mechanism is still unclear. We assessed the influences of morin on cell viability, colony formation, and migration ability of A549 and employed microRNA array to identify the microRNAs affected by morin. We found that morin-treated A549 cells showed statistically decreased cell viability, colony formation, and migration rate when comparing with the dimethyl sulfoxide-treated cells. Microarray results showed that with the treatment of morin, the expression level of miR-135b significantly reduced compared the control group, suggesting that morin may exert its anti-cancer property by suppressing the expression of miR-135b. In addition, we found a potential binding site of miR-135b within 3' untranslated region of CCNG2-encoding cyclin homolog cyclin-G2. We evidenced that miR-135b directly targets CCNG2, which could be a potential biomarker of lung cancer prognosis. Morin exerts its anti-tumor function via downregulating the expression of miR-135b that directly targets and represses CCNG2.


Filling of the central intrarenal veins during retrograde pyelography following a recent kidney transplantation. Report of a case.
During routine retrograde pyelography in a recently transplanted kidney filling of the central intrarenal veins was observed. This unique radiologic picture was due to renal vein thrombosis. The case is discussed in relation to previous experimental findings.


Are isolated facial cleft lip and palate associated with increased perinatal mortality? A cohort study from the West Midlands Region, 1995-1997.
To investigate the association between cleft lip and/or palate and perinatal mortality. A retrospective review was performed of cases of cleft lip/palate born to West Midlands residents from 1995 to 1997. Perinatal mortality for identified cases was compared with all births from 1995 to 1997. 347 cases of cleft lip and/or cleft palate were delivered from 1995 to 1997. Thirty-six pregnancies were terminated due to parental wishes--2 were registerable births. There were 310 spontaneous registerable births (stillbirths/livebirths) with cleft lip and/or palate and 1 further late fetal loss. In 220 (70.5%), the lesion was isolated. Of these, there were 7 perinatal deaths, 5 had post mortems and no additional anomalies were identified. In 92 (29.5%) cases other abnormalities were identified. The overall perinatal mortality rate (PNMR) in the West Midlands, was 10.0/1000 total births. The overall PNMR for babies with facial clefts was 89.7/1000 total births. The PNMR for those with associated anomalies was 228.3/1000 live/still births. The PNMR for isolated facial clefts was 31.8/1000 live/still births, significantly higher than the background population (OR 3.3, 95% CI: 1.5-7.0). Consideration should be given to screening the fetus at 20-24 weeks for facial deformity. This has implications for detection both of fetal anomalies and of a population at risk for adverse outcome.


Microbially corrected amino acid composition of rumen-undegraded feed protein and amino acid degradability in the rumen of feeds enclosed in nylon bags.
1. In the previous work (Varvikko & Lindberg, 1985), 15N-labelled rapeseed (Brassica napus), barley, ryegrass (Lolium perenne) and barley straw were incubated in the rumen in nylon bags for 5, 12 and 24 h and microbial nitrogen in the residues was quantified using the feed 15N-dilution method. In the present study, residual amino acids (AA) of these feeds were analysed, and microbially corrected AA of feed origin (feed AA) were estimated as the difference between total residual AA and respective microbial AA, assuming a constant AA composition for the microbial protein. 2. In barley and barley-straw residues, and also in ryegrass incubated in the rumen for 24 h, very large enrichment by microbial N and AA-N was found. The microbial enrichment was rather small in rapeseed residues and ryegrass incubated for 5 or 12 h. During the rumen incubation, feed N and AA-N (g/kg feed dry matter (DM] decreased very clearly in all the feeds, and feed and incubation time effects were always statistically significant (P less than 0.001). 3. The slow degradation of essential (E) feed AA compared with the respective non-essential (NE) AA degradation increased the proportion of feed EAA (g/kg determined feed AA) in barley and barley-straw residues. In rapeseed and ryegrass, residual feed EAA:NEAA remained very similar to the original. Branched-chain (Br) AA tended to increase proportionally in all the feed residues, suggesting these AA to be, on average, more resistant against microbial degradation in the rumen than other AA. Similarly, lysine was clearly increased in barley residues. A rumen degradation faster than the average rate caused decreased residual feed glutamic acid in rapeseed; methionine, alanine and glycine in barley; arginine and alanine in ryegrass; and methionine, asparagine and tyrosine in barley straw. Feed and incubation time effects were significant (P less than 0.05-0.001) for feed AA (g/kg determined feed AA) grouped as EAA, BrAA or NEAA, and for most individual AA, as well as for feed AA disappearance (%) and relative amounts (%) of feed AA in the respective residual AA. 4. According to present findings, AA composition of the rumen-degraded vegetable feed residues may markedly differ, either quantitatively or qualitatively (or both), from their original AA composition. When determining the feed AA composition of nylon-bag residues, the microbial error may be very large with starchy or fibrous feeds of low protein content. The microbial AA do not, however, considerably confuse the AA determination of protein-rich feeds.


Colocalisation of taurine- with transmitter-immunoreactivities in the nervous system of the migratory locust.
The expression of taurine immunoreactivity (TAU-IR) by neurones immunoreactive for octopamine (OA-IR), gamma-aminobutyric acid (GABA-IR), and the C-terminal peptide sequence arginine-phenylalanine (RFamide-IR) was investigated in the migratory locust (Locusta migratoria). TAU-IR is colocalised with OA-IR in the dorsal unpaired median neurones, which are efferent neuroparacrine cells. TAU-IR is not, however, expressed by OA-IR interneurones in the thoracic ganglia and brain. The only other TAU-IR somata found with peripheral axons are the medial neurosecretory cells in abdominal ganglia that project to the neurohaemal organs. These cells exhibit RFamide-IR. The majority of TAU-IR somata in the thoracic abdominal nervous system exhibit GABA-IR. These cells correspond to populations of identified local and intersegmentally projecting inhibitory interneurones. TAU-IR is not, however, exhibited by the well-known GABAergic common inhibitor neurones, which have peripherally projecting axons. This differential distribution of TAU-IR in basically two, functionally different, neuronal subsets (efferent neurosecretory and neuroparacrine cells, inhibitory interneurones) conforms with the concept of taurine acing as a depressive agent to limit excitation during stressful conditions.


Large cell lymphoma presenting as a coronal penile lesion.
Although the majority of penile malignancies are primary epithelial carcinomas, consideration of secondary involvement, especially from lymphoma, is important, since there are alternatives to the standard therapeutic approach of penile amputation.


FDA Warning Letters: A Retrospective Analysis of Letters Issued to Pharmaceutical Companies from 2010-2020.
To launch a pharmaceutical product in the US market, approval from the FDA is required. Pharmaceutical companies undergo FDA pre-approval inspection (PAI for small molecule products) or pre-license approval (PLI for biological products) at their manufacturing sites (including contract development and manufacturing organization, testing laboratories, and packaging labelling facilities) prior to approval. After the products are approved by the FDA, surveillance inspections are performed by the FDA which are risk based as which company and which site will be inspected. The present study examines the causes of warning letters issued by the Center for Drug Evaluation and Research (CDER), FDA to the pharmaceutical companies after post-approval inspections. Warning letters issued from the time period 2010 to 2020 were obtained from the FDA website, and information about date of issuance, company, and type of violations was extracted for the study. Poor compliance to CGMP and misbranding were the most common reasons for the warning letters. Detailed analysis of CGMP warning letters elucidated three major types of violations, namely deficiencies in process validation, documentation practices (data integrity), and quality control corresponding to 26%, 21%, and 15% warning letters, respectively. Review of the analysed letters demonstrates that the FDA's major concern is over CGMP compliance. To avoid these warning letters, pharmaceutical manufacturers need to improve their quality compliance and focus on creating effective quality management systems that govern the entire manufacturing process, quality control, employee training, and documentation practice. Companies should develop an internal compliance check list and also be ready for corrective measures as and when required. The online version contains supplementary material available at 10.1007/s12247-022-09678-2.


The evolution of gonadotropins: some molecular data concerning a non-mammalian pituitary gonadotropin, the hormone from a teleost fish (Cyprinus carpio L.).
The amino acid and sugar compositions as well as long N-terminal sequences and the C-terminal amino acids of the two subunits of carp gonadotropin, SU I and SU II, were determined. An important homology was demonstrated between SU I and alpha-subunits and between SU II and beta-subunits of mammalian gonadotropins. Moreover SU II was more closely related to the beta-subunit of LH than to the beta-subunit of FSH.


Retracted: Analysis of Factors Related to Adolescents' Physical Activity Behavior Based on Multichannel LSTM Model.
[This retracts the article DOI: 10.1155/2022/1022421.].


The fiber projections from the dentate nucleus to the reticular formation of the brain stem in the rabbit.
The projections from the dentate nucleus to the reticular formation of the brain stem in rabbit have been examined by means of the Fink-Heimer technique. The fibers arising from the dentate nucleus primarily project to the reticular formation via the contralateral and ipsilateral descending limbs of the brachium conjunctivum. The descending fibers project bilaterally to the parvocellular reticular nucleus, the ventral reticular nucleus, the gigantocellular reticular nucleus, the nucleus raphe magnus, the oral and caudal pontine reticular nuclei, and the reticulo-tegmental nucleus.


Assessment of human colorectal biopsies by 1H MRS: correlation with histopathology.
Samples (3 mm3) of histopathologically normal (n = 15) and carcinomatous tissue (n = 15) were obtained from colectomy specimens and examined by 1H MRS. A combination of one- and two-dimensional spectra, obtained with appropriate acquisition and processing parameters, provide multiple diagnostic parameters allowing the distinction between normal and carcinomatous tissue. The diagnostic parameters include resonances from choline, choline-based, and other metabolites, cell surface fucosylation, and altered lipid profiles. Tissues histopathologically classified as normal, while remaining distinct from the malignant spectral profile, were found to fit into two categories, one of which had some of the spectral characteristics of malignancy. These results indicate that 1H MRS identifies abnormal colorectal mucosa, which is not morphologically manifest. Such abnormalities have been reported previously to exist in premalignant colorectal tissue by monoclonal antibody studies. Collectively, these results suggest that a clinical study of colorectal biopsies by 1H MRS could provide support for the use of MRS as an adjunct to current pathological procedures.


Morphometric investigations on endocrine glands. III. The effect of turisynchron and suisynchron on the thyroid gland of the Wistar rats.
Karyometric and morphometric investigations on the thyroids of Wistar rats had the following results: complexing of methallibure (Turisynchron) with zinc lowers the inhibiting action of the parent substance on the thyroid in a short time test period.


Mechanisms of disease: motoneuron disease aggravated by transgenic expression of a functionally modified AMPA receptor subunit.
To reveal whether increased Ca2+ permeability of glutamate AMPA channels triggered by the transgene for GluR-B(N) induces decline in motor functions and neurodegeneration in the spinal cord, we evaluated growth, motor coordination, and spinal reflexes in transgenic GluR-B(N) and wild-type (wt) mice. To reveal whether the transgenic GluR-B(N) expression aggravates the course of motoneuron disease in SOD1 mice, we mated heterozygous GluR-B(N) and SOD1 [C57BL6Ico-TgN(hSOD1-G93A)1Gur] mice to generate double-transgenic progeny. The phenotypic sequelae in mice carrying mutations were evaluated by monitoring growth, motor coordination, and survival. Neuronal degeneration was assessed by morphological and stereological analysis of spinal cord and brain. We found that transgenic expression in mice of GluR-B(N)-containing glutamate AMPA receptors with increased Ca2+ permeability leads to a late-onset degeneration of neurons in the spinal cord and decline of motor functions. Neuronal death progressed over the entire life span, but manifested clinically in late adulthood, resembling the course of a slow neurodegenerative disorder. Additional transgenic expression of mutated human SOD1 accelerated disease progression, aggravated severity of motor decline, and decreased survival. These observations reveal that moderate, but persistently elevated Ca2+ influx via glutamate AMPA channels causes degeneration of spinal motoneurons and motor decline over the span of life. These features resemble the course of sporadic amyotrophic lateral sclerosis (ALS) in humans and suggest that modified function of glutamate AMPA channels may be causally linked to pathogenesis of ALS.


A three-species synthetic community model whose rapid response to antagonism allows the study of higher-order dynamics and emergent properties in minutes.
Microbial communities can be considered complex adaptive systems. Understanding how these systems arise from different components and how the dynamics of microbial interactions allow for species coexistence are fundamental questions in ecology. To address these questions, we built a three-species synthetic community, called BARS (Bacillota A + S + R). Each species in this community exhibits one of three ecological roles: Antagonistic, Sensitive, or Resistant, assigned in the context of a sediment community. We show that the BARS community reproduces features of complex communities and exhibits higher-order interaction (HOI) dynamics. In paired interactions, the majority of the S species (Sutcliffiella horikoshii 20a) population dies within 5 min when paired with the A species (Bacillus pumilus 145). However, an emergent property appears upon adding the third interactor, as antagonism of species A over S is not observed in the presence of the R species (Bacillus cereus 111). For the paired interaction, within the first 5 min, the surviving population of the S species acquires tolerance to species A, and species A ceases antagonism. This qualitative change reflects endogenous dynamics leading to the expression for tolerance to an antagonistic substance. The stability reached in the triple interaction exhibits a nonlinear response, highly sensitive to the density of the R species. In summary, our HOI model allows the study of the assembly dynamics of a three-species community and evaluating the immediate outcome within a 30 min frame. The BARS has features of a complex system where the paired interactions do not predict the community dynamics. The model is amenable to mechanistic dissection and to modeling how the parts integrate to achieve collective properties.


Transcatheter aortic valve replacement after chest radiation: A propensity-matched analysis.
Chest radiation therapy (CRT) for malignant thoracic neoplasms is associated with development of valvular heart disease years later. As previous radiation exposure can complicate surgical treatment, transcatheter aortic valve replacement (TAVR) has emerged as an alternative. However, outcomes data are lacking for TAVR patients with a history of CRT. We conducted a retrospective study of all patients who underwent a TAVR procedure at a single institution between September 2012 and November 2018. Among 1341 total patients, 50 had previous CRT. These were propensity-matched in a 1:2 ratio to 100 patients without history of CRT. Thirty-day adverse events were analyzed with generalized estimating equation models. Overall mortality was analyzed with stratified Cox regression modelling. Median clinical follow-up was 24 months (interquartile range [IQR], 12-44 months). There was no difference between CRT and non-CRT patients in overall mortality (hazard ratio [HR] 0.84 [0.37-1.90], P = 0.67), 30-day mortality (HR 3.1 [0.49-20.03], P = 0.23), or 30-day readmission rate (HR 1.0 [0.43-2.31], P = 1). There were no differences in the rates of most adverse events, but patients with CRT history had higher rates of postprocedural respiratory failure (HR 3.63 [1.32-10.02], P = 0.01) and permanent pacemaker implantation (HR 2.84 [1.15-7.01], P = 0.02). For patients with aortic valve stenosis and previous CRT, TAVR is safe and effective, with outcomes similar to those in the general aortic stenosis population. Patients with history of CRT are more likely to have postprocedural respiratory failure and to require permanent pacemaker implantation.


Long-term correlates of childhood abuse among adults with severe mental illness: adult victimization, substance abuse, and HIV sexual risk behavior.
The prevalence of childhood sexual and physical abuse among persons with severe mental illness (SMI) is disproportionately high. Adults with SMI also engage in high rates of HIV risk behaviors. This study examined the association between childhood abuse and adult victimization, substance abuse, and lifetime HIV sexual risk in a sample of 152 adults with SMI receiving community mental health services. Structured interviews assessed psychiatric, psychosocial, and behavioral risk factors. Seventy percent reported childhood physical and/or sexual abuse, and 32% reported both types of abuse. Participants with childhood abuse were more likely to report adult victimization and greater HIV risk. A structural equation model found that childhood abuse was directly and indirectly associated with HIV risk through drug abuse and adult vicitimization. Integrated treatment approaches that address interpersonal violence and substance abuse may be necessary for HIV risk reduction in this population.


Development of an Integrated Mobile Application for Evaluating Voiding Dysfunction: A Proof of Concept Study.
Bladder voiding diaries are an important part of evaluating and managing lower urinary tract symptoms but are subject to poor data quality and diary completion rates. Mobile health technology is increasingly prevalent and can help overcome the problems of traditional paper and electronic diaries. We identified proof of concept design principles based on a literature review and needs assessment. An electronic application was developed to improve self-assessment and symptom management for patients with voiding dysfunction. We analyzed application distribution and use patterns for 12 consecutive months. We designed an electronic application with complete mobile device integration containing a voiding diary, incontinence tracker and AUA Symptom Score questionnaire. Users could enter and modify details about the volume and frequency of voiding events, including leakage and pad use. Data could be electronically shared with providers. Integrating the application on the Apple® iOS and Android™ mobile operating systems eliminated the need for patients to carry or learn to use a separate device. During the 12-month study period 1,868 unique visitors from 18 countries downloaded the mobile application and made a total of 13,145 subsequent visits. This application for evaluating voiding dysfunction leverages mobile technology to overcome the limits of paper and standalone electronic formats. Domestic and international users downloaded the application and consistently logged return visits. Using mobile health in urology practices may help patients and providers better manage lower urinary tract symptoms and achieve improved control.


Bowel Preparation With Polyethylene Glycol 3350 or Fasting Only Before Peroral Single-balloon Enteroscopy: A Randomized European Multicenter Trial.
Although bowel preparation before colonoscopy and capsule endoscopy is widely evaluated and usually follows established guidelines, a standard preparation regime for peroral small bowel enteroscopy is yet to be defined.The aim of the present study was to compare small bowel preparation with polyethylene glycol (PEG) and "fasting only" (FO) before peroral single-balloon enteroscopy (SBE). We compared small bowel preparation with PEG versus "FO" for peroral SBE in a randomized European multicenter trial. Patients' and procedural characteristics were documented and carefully analyzed. Primary endpoint was the oral intubation depth of the small bowel. A modified Boston preparation scale was used to assess bowel cleansing as a secondary endpoint. In total, 43 patients were enrolled in this study (FO group: n=25; PEG group: n=18). In both groups, patients' characteristics were comparable. The indications for oral enteroscopy were equally distributed in both groups (P=0.894). The oral intubation depth was significantly higher in the PEG versus the FO group (261±87 vs. 203±66 cm; P=0.019; mean±SD), while the quality of bowel preparation was equally sufficient in both groups [complete visualization of the mucosa (Boston preparation scale) 83% versus 76% (P=1.000)]. Small bowel preparation with PEG for SBE yields significantly deeper intubation as compared with "FO" preparation. As patient comfort and safety was similar in both groups, PEG preparation might be favored, especially if deep intubation of the small bowel is desired. For patients requiring visualization of the proximal jejunum, a FO preparation seems to be sufficient.


Is early integration of palliative home care in oncology treatment feasible and acceptable for advanced cancer patients and their health care providers? A phase 2 mixed-methods study.
To support the early integration of palliative home care (PHC) in cancer treatment, we developed the EPHECT intervention and pilot tested it with 30 advanced cancer patients in Belgium using a pre post design with no control group. We aim to determine the feasibility, acceptability and perceived effectiveness of the EPHECT intervention. Interviews with patients (n = 16 of which 11 dyadic with family caregivers), oncologists and GPs (n = 11) and a focus group with the PHC team. We further analyzed the study materials and logbooks of the PHC team (n = 8). Preliminary effectiveness was assessed with questionnaires EORTC QLQ C-30, HADS and FAMCARE and were filled in at baseline and 12, 18 and 24 weeks. In the interviews after the intervention period, patients reported feelings of safety and control and an optimized quality of life. The PHC team could focus on more than symptom management because they were introduced earlier in the trajectory of the patient. Telephone-based contact appeared to be insufficient to support interprofessional collaboration. Furthermore, some family caregivers reported that the nurse of the PHC team was focused little on them. Nurses of PHC teams are able to deliver early palliative care to advanced cancer patients. However, more attention needs to be given to family caregivers as caregiver and client. Furthermore, the home visits by the PHC team have to be further evaluated and adapted. Lastly, professionals have to find a more efficient way to discuss future care.


Medial Column Biomechanics: Nonsurgical and Surgical Implications.
Understanding of medial column biomechanics is paramount to a successful outcome in both conservative and surgical treatment. Dysfunctions of the dynamic stabilizers as well as the static stabilizers of the medial column play a role in pathomechanics. Conservative options for addressing the medial column include custom foot orthotics and bracing. Options for addressing the medial column surgically with the goal to restore a stable tripod configuration, include first tarsometatarsal joint arthrodesis, opening plantarflexory medial cuneiform osteotomy, and naviculocuneiform arthrodesis.


[Psychodynamic aspects of depression and suicidal behavior in childhood and adolescence--with reference to the monograph by Hermann Emminghaus 1887].
The centenary of the first monograph on children psychiatry gives occasion to stress the topicality of a syndrome-oriented children and youth psychopathology, as well as the special importance of anxiety symptomatology as an index symptom of depressive interrelational disorders within the psycho-social field of experience during development. The paper discusses both multi-dimensional and psychodynamic approaches.


Normal and benzo(a)pyrene-transformed fetal mouse brain cell. I. Tumorigenicity and immunochemical detection of glial fibrillary acidic protein.
Primary cultures of whole brain and cortex cells origination from 14-day-old A/Jax or C3H mouse fetuses were treated with benzo(a)pyrene (B(a)P) for 24 h. After 7 to 8 passages a malignant transformation was observed in the chemically treated whole brain and cortex cultures. Control cultures of cortex remained non-transplantable during the whole experiment (up to 14 passages) whereas in the control cultures originating from whole brain a spontaneous transformation appeared after 11 passages. With horseradish peroxidase-labelled antibody, the specific glial fibrillary acidic protein (GFAP) was detected in both control and transformed total brain and cortex cultures, and in the tumors initiated by the in vitro transformed cells. This finding shows that glialike cells persisted after a long in vitro maintanance and transformation.


Suspended judgment. AIDS and the ethics of clinical trials: learning the right lessons.
There is a tribe of thinkers who believe that new technological advances and scientific discoveries raise new ethical issues. And it is the case, of course, that scientific and technological change--change in knowledge and power--implies a new realm for choice and, therefore, moral reflection. In the case presently concerning us, they see the AIDS social and scientific crisis as requiring the adoption of new ethical principles. I believe to the contrary. AIDS--more broadly, the entire spectrum of HIV disease--does not in itself present radically new issues at the level of principle. For example, the questions associated with confidentiality and HIV disease that have to this point dominated public discourse about morality and AIDS simply resurrect old questions raised by potentially deadly infectious disease. Recent discussions of the ethical issues associated with HIV-infectious health care workers fail to recognize that HIV is simply a new garb for the old question of the impaired or unsafe practitioner. HIV disease does have this effect on ethical reflection, however: It rubs our noses in issues that may have received insufficient attention to date. The urgency and poignancy associated with moral conflict and HIV disease forces us to face up to questions hitherto ignored. But this may be a good or a bd thing. In the heat of crisis, being human, we are likely to call for change without adequate consideration of the need for and effects of that change.(ABSTRACT TRUNCATED AT 250 WORDS)


Spontaneous aortic laceration causing flail aortic valve and acute aortic regurgitation.
Spontaneous laceration of the aorta is an unusual cause of flail aortic valve. We report a case of acute aortic regurgitation caused by flail aortic valve as a result of spontaneous laceration of the ascending aorta. The role of transesophageal echocardiography in the diagnosis of this condition is discussed.


Reevaluating leishmanin skin test as a marker for immunity against cutaneous leishmaniasis.
The leishmanin skin test (LST) has been used for clinical diagnosis of leishmaniasis and epidemiological studies of the disease. Thus far, evidence has suggested that LST conversion indicates a degree of protection against leishmaniasis. In this study, we have put this assumption to test. A total of 273 participants with positive LST living in a hyperendemic area for leishmaniasis were followed for three years for any occurrence of cutaneous leishmaniasis. Twenty-two of the 273 participants contracted leishmaniasis during the 3-year follow-up. These new cases included participants who had a previous history of active disease, those who had a history of leishmanization, or those who were suspected of having a history of subclinical infection. In this study, the incidence of leishmaniasis in individuals with positive LST was close to the general incidence of the disease in the same hyperendemic area. These results suggest that although LST conversion may be a marker for partial immunity towards leishmaniasis, it may not, however, indicate complete protection against the disease, and consequently there is a need for revision of current vaccine development approaches which are based on rendering vaccinated individuals LST positive.


Indications for nephrectomy in children: what has changed?
To review the indications for nephrectomy in children between 1990 and 2001, at the Starship Children's Hospital, Auckland, New Zealand. There were 206 nephrectomies. A retrospective review of the patients' notes was performed. The 12-year period was divided into two halves (1990-1996 and 1996-2001) which were then compared. The total number of nephrectomies per year significantly increased over the period of the study (11.5 and 22.2 per year for 1990-1995 and 1996-2001, respectively; P<0.05), as did the number of partial nephrectomies (one and 23 for 1990-1995 and 1996-2001, respectively; P<0.01). Multicystic dysplastic kidney (MCDK), Wilms' tumour and vesico-ureteric reflux (VUR) accounted for more than half of the nephrectomies (60% and 68% for 1990-1995 and 1996-2001, respectively). The proportion of nephrectomies performed for these indications did not change (MCDK 25% and 34%, Wilms' 25% and 18%, VUR 16% and 18%, for 1990-1995 and 1996-2001, respectively), but fewer nephrectomies were performed for pelvi-ureteric junction (PUJ) obstruction in the second half of the study period (13% and 4% for 1990-1995 and 1996-2001, respectively; P<0.05). The total number of nephrectomies, including partial nephrectomies, has increased significantly. The decrease in nephrectomies for PUJ obstruction could be accounted for by a more aggressive approach in the management and follow up of prenatally diagnosed hydronephrosis. Of note is that there was no significant change in the proportion of nephrectomies performed for Wilms' tumour, MCDK and VUR.


High-resolution 64-slice helical-computer-assisted-tomographical-angiography as a diagnostic tool before CABG surgery: the dawn of a new era?
For the first time, technical developments in helical, high-resolution 64-slice computer-assisted-tomographical-scanning (CT) allows for analysis of cardiac pathology including coronary morphology. Here, we present results of a multicenter study assessing the value CT-angiography as a preoperative diagnostic tool in identifying target vessels for coronary artery bypass grafting (CABG) surgery. Thirty-two patients aged 64+/-9.0 years, 30 with confirmed coronary disease (angiography or scintigraphy) and 2 controls, underwent helical CT analysis. Scans were reviewed in a blinded fashion and potential target vessels for CABG were identified by seven individual reviewers. Results were compared with those from conventional coronary angiography and with the target vessels chosen at surgery. Results showed a high positive predictive value for targeting at surgery, which was comparable for both conventional angiography and CT scan (LAD 100% vs 97%, RCx 96% vs 93%, 67% vs 56%). In one patient, who presented with clinical signs of CAD and positive scintigraphy results, conventional angiography revealed no stenotic lesion and CT scan was used to confirm main stem disease. CT-angiography sufficiently allows for target vessel determination for CABG. In individual cases, visual assessment of the left main coronary artery and the proximal left anterior descending artery (LAD) via CT-angiography may be superior to conventional angiography. However, while there is no difference in positive predictive targeting value, sensitivity and specificity of conventional angiography is still superior. Also, improvements in the methodology of evaluation and presentation of CT-findings are necessary. Our data suggest that CT-angiography may be used as a clinical alternative to conventional angiography in preoperative assessment for cardiac surgery.


Targeting ARF1-IQGAP1 interaction to suppress colorectal cancer metastasis and vemurafenib resistance.
Acquired resistance to BRAF inhibitor vemurafenib is frequently observed in metastatic colorectal cancer (CRC), and it is a thorny issue that results in treatment failure. As adaptive responses for vemurafenib treatment, a series of cellular bypasses are response for the adaptive feedback reactivation of ERK signaling, which warrant further investigation. We identified ARF1 (ADP-ribosylation factor 1) as a novel regulator of both vemurafenib resistance and cancer metastasis, its molecular mechanism and potential inhibitor were investigated in this study. DIA-based quantitative proteomics and RNA-seq were performed to systematic analyze the profiling of vemurafenib-resistant RKO cells (RKO-VR) and highly invasive RKO cells (RKO-I8), respectively. Co‑immunoprecipitation assay was performed to detect the interaction of ARF1 and IQGAP1 (IQ-domain GTPase activating protein 1). An ELISA-based drug screen system on FDA-approved drug library was established to screen the compounds against the interaction of ARF1-IQGAP1.The biological functions of ARF1 and LY2835219 were determined by transwell, western blotting, Annexin V-FITC/PI staining and in vivo experimental metastasis assays. We found that ARF1 strongly interacted with IQGAP1 to activate ERK signaling in VR and I8 CRC cells. Deletion of IQGAP1 or inactivation of ARF1 (ARF-T48S) restored the invasive ability induced by ARF1. As ARF1-IQGAP1 interaction is essential for ERK activation, we screened LY2835219 as novel inhibitor of ARF1-IQGAP1 interaction, which inactivated ERK signaling and suppressed CRC metastasis and vemurafenib-resistance in vitro and in vivo with no observed side effect. Furthermore, LY2835219 in combined treatment with vemurafenib exerted significantly inhibitory effect on ARF1-mediated cancer metastasis than used independently. This study uncovers that ARF1-IQGAP1 interaction-mediated ERK signaling reactivation is critical for vemurafenib resistance and cancer metastasis, and that LY2835219 is a promising therapeutic agent for CRC both as a single agent and in combination with vemurafenib.


Prognostic Implication of a Metabolism-Associated Gene Signature in Lung Adenocarcinoma.
Lung cancer is the most common cancer worldwide, leading to high mortality each year. Metabolic pathways play a vital role in the initiation and progression of lung cancer. We aimed to establish a prognostic prediction model for lung adenocarcinoma (LUAD) patients based on a metabolism-associated gene (MTG) signature. Differentially expressed (DE)-MTGs were screened from The Cancer Genome Atlas (TCGA) LUAD cohorts. Univariate Cox regression analysis was performed on these DE-MTGs to identify genes significantly correlated with prognosis. Least absolute shrinkage and selection operator (LASSO) regression was performed on the resulting genes to establish an optimal risk model. Survival analysis was used to assess the prognostic ability of the model. The prognostic value of the gene signature was further validated in independent Gene Expression Omnibus (GEO) datasets. A gene signature with 13 metabolic genes was identified as an independent prognostic factor. Kaplan-Meier survival analysis demonstrated the good performance of the risk model in both TCGA training and GEO validation cohorts. Finally, a nomogram incorporating clinical parameters and the metabolic gene signature was constructed to help individualize outcome predictions. The calibration curves showed excellent agreement between the actual and predicted survival.


Reaction characteristics of andrographolide and its analogue AL-1 with GSH, as a simple chemical simulation of NF-κB inhibition.
14-α-Lipoic acid-3,19-dihydroxyandrographolide (AL-1, 2) is an analogue of andrographolide (Andro, 1) coupled to α-lipoic acid (LA, 4). AL-1 was at least 10-fold more potent than the natural parent compound Andro in inhibiting nuclear factor (NF)-κB activation in RIN-m cells. In the present study, glutathione (GSH, 3) was used as a simple chemical model molecule of NF-κB with cysteine 62. The characteristics of the reaction between AL-1 or Andro and GSH were investigated to trace some possible elucidation for the inhibitive mechanism and stronger inhibition of AL-1 to NF-κB activation. The results showed that the main reaction products of AL-1 and Andro were identical, sulfhydryl adduct and amino adduct. AL-1 reacted much faster than Andro with GSH. The product yield of AL-1 was much higher than that of Andro. It was speculated that AL-1 might inhibit NF-κB by the same mechanism as Andro. And the faster reaction rate and higher yield may account for the stronger NF-κB inhibition of AL-1 when compared with Andro.


[Pain patterns of disc lesions of the lumbar spine].
The aim of this study was to find out the reliability of several dermatomic maps (description of pain pattern within a nerve root lesion) according to the respective segmental area. Different studies which deal with pain pattern caused by disc lesions were searched for with MedLine support and then reviewed. A clear correlation between the pain projections of the lumbar spine does not seem to exist. A contradiction of the most common pain projection (S1) and operated disc (L4/5) is described. Even though there are studies of high scientific design and value (Nitta H, Wolff A) the pain pattern of dermatomic maps is only of limited value for the definition of the affected segment.


Eicosanoid-induced growth and signaling events in rat glomerular mesangial cells.
Renal glomerular injury frequently results in proliferation of a specialized supporting cell of the glomerular capillary known as the mesangial cell. In various forms of renal injury there is enhanced glomerular synthesis of specific eicosanoids of the arachidonic cyclooxygenase and lipoxygenase pathways including prostaglandin (PG) F2 alpha, thromboxane (Tx) A2, the hydroxyeicosatetraenoic acids 12-HETE and 5-HETE, and the leukotrienes LTB4 and LTD4 and attempts have been made to link these eicosanoids with injury-induced mesangial cell growth. In this study, the growth promoting effect of these eicosanoids on glomerular mesangial cells was correlated with activation of two growth regulatory enzymes: phospholipase C (PLC) and protein kinase C (PKC). PGF2 alpha, and TxA2 endoperoxide analog U-46619, and LTD4 significantly enhanced DNA synthesis [(as assessed by [3H]thymidine (TdR) incorporation)] in relatively quiescent (0.5% serum) mesangial cells, activated PLC [as assessed by increased 1,4,5-inositol tris-phosphate (IP3) generation and diacylglycerol (DAG) synthesis], and activated PKC (as assessed by translocation of the enzyme activity from the cytosol to the membrane). The effect of PGF2 alpha on IP3 generation was not blocked by the TxA2 receptor antagonist, SQ-29,548. PGF2 alpha was the most effective eicosanoid in inducing all three events, and concentrations that enhanced TdR incorporation (1 microM) also activated PLC and PKC. In contrast, concentrations of U-46619 and LTD4 which enhanced TdR incorporation (1 microM), also activated PLC, but were insufficient to also activate PKC. Our observations indicate that the growth-promoting effect of PGF2 alpha, U-46619, and LTD4 can best be correlated with PLC activation. In addition, PGF2 alpha does not mediate PLC activation through binding to the TxA2 receptor.


Microhabitat use by bisexual and unisexual fishes (Poeciliopsis: Poeciliidae) in an artificial stream.
Two all-female species of viviparous fish depend on males of bisexual species for sperm in order to reproduce. The unisexual P. monacha-latidens mates with males of P. latidens (the sexual host) while the unisexual P. monacha-lucida mates with males of P. lucida (its sexual host). Ecological divergence of each unisexual from its sexual host is promoted by any competitive interactions while ecological convergence of the unisexual toward its sexual host is promoted by the unisexual's sperm requirements. This study measured the habitat use in an artificial stream of five Poeciliopsis species (P. monacha-latidens, P. monacha-lucida, P. latidens, P. lucida and P. monacha) when alone and in several combinations. The habitat use of both unisexuals was examined for evidence of 1) competition with their sexual hosts, 2) use of monacha-like behavior, and 3) competition with each other. The two unisexuals interacted differently with their sexual hosts. P. monachalatidens competed with P. latidens. These two species differed more in their habitat use when they were sympatric than when they were allopatric. They frequented different habitats when they were sympatric, P. latidens preferring fast-water areas and P. monacha-latidens preferring slowwater areas. The distribution of P. monacha-latidens was more similar to P. monacha when the unisexual was with its sexual host than when it was alone, indicating that this unisexual may use monacha-like behavior to escape from competition with its sexual host. In contrast, P. monachalucida did not compete with P. lucida. These two species were more similar in their habitat use when they were sympatric than when they were allopatric. The habitat use of P. monacha-lucida when alone and when with P. lucida showed no consistent pattern when compared with the habitat use of P. monacha. Apparently, P. monacha-lucida did not use monacha-like behavior when with its sexual host. The two unisexuals did not compete. Thus, forces favoring ecological divergence are more important for P. monachalatidens and forces favoring ecological convergence are more important for P. monacha-lucida.


Respiratory complications following cardiac surgery. The role of microbiology in its evaluation.
Sputum specimens were received for microbiological examination from 110 patients following open heart surgery. The isolation of Haemophilus influenzae occurred significantly more often in those patients who had pre-existing chest disease, but was not associated with postoperative chest problems. There was a significant association between pre-operative heart failure and subsequent severe pulmonary complications.


What Mesh Should be Used in Hernia Repair?
Ventral hernia repair is one of the most frequently performed general surgery operations in the world, yet the treatment of clean-contaminated and contaminated cases remains controversial. Biologic mesh has been thought to resist infection, decrease chronic wound complications, and reduce the need for reoperation. Their use continues to be predominant in contaminated and dirty cases. This article is a comprehensive review of what mesh to choose in both clean and contaminated single-staged, open ventral hernia repair with further considerations of tissue incorporation characteristics, cost, safety profiles, complications, recurrence, and long-term outcomes.


Structural and functional characterization of D109H and R69C mutant versions of human αB-crystallin: The biochemical pathomechanism underlying cataract and myopathy development.
In human αB-crystallin (αB-Cry), the highly conserved residues arginine 69 (R69) and aspartate 109 (D109) are located within a critical motif of α-crystallin domain (ACD), contributing to the subunit interactions and oligomeric assembly. Recently, two missense mutations (R69C and D109H) in human αB-Cry have been reported to cause congenital cataract and myopathy disorders. We used various spectroscopic techniques, dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), gel electrophoresis and transmission electron microscopy (TEM) to show how these mutations cause significant changes in structure, amyloidogenic feature and biological function of human αB-Cry. These pathogenic mutations resulted in the important alterations of the secondary, tertiary and oligomeric (quaternary) structures of human αB-Cry. The missense mutations were also capable to significantly increase the amyloidogenic propensity of human αB-Cry and to diminish the chaperone-like activity of this protein. The above mentioned changes were observed more noticeably after D109H mutation. The detrimental effects of D109H mutation may be due to the loss of salt bridge with R120 in the dimeric interface, flagging the anti-aggregation ability of αB-Cry chaperone. In conclusion, the R69C and D109H mutations displayed a significant damaging effect on the structure and chaperone function of human αB-Cry which could be considered as their biochemical pathomechanisms in development of congenital cataract and myopathy disorders.


Depositional environment and geochemical response of mangrove sediments from creeks of northern Maharashtra coast, India.
Present study provides results of trace metal distribution in mangrove sediment cores collected from macro-tidal Khonda and Dudh creeks of Northern Maharashtra coast, India. Most of the metals showed significant higher addition in Dudh creek (core DC) as compared to Khonda creek (core KC). However, Khonda creek sediments did show anthropogenic enrichment of Mn, Zn and Ni, while Dudh creek sediments showed anthropogenic enrichment of almost all the studied metals. Large difference in metal concentration between the two creeks was attributed to their proximity to industries. The higher Mn, Zn and Ni content in Khonda creek was mainly attributed to addition from domestic and agricultural wastes. While high deterioration of Dudh creek sediments was the outcome of addition from industrial effluents.


Sequential cytarabine and alpha-particle immunotherapy with bismuth-213-lintuzumab (HuM195) for acute myeloid leukemia.
Lintuzumab (HuM195), a humanized anti-CD33 antibody, targets myeloid leukemia cells and has modest single-agent activity against acute myeloid leukemia (AML). To increase the potency of the antibody without the nonspecific cytotoxicity associated with β-emitters, the α-particle-emitting radionuclide bismuth-213 ((213)Bi) was conjugated to lintuzumab. This phase I/II trial was conducted to determine the maximum tolerated dose (MTD) and antileukemic effects of (213)Bi-lintuzumab, the first targeted α-emitter, after partially cytoreductive chemotherapy. Thirty-one patients with newly diagnosed (n = 13) or relapsed/refractory (n = 18) AML (median age, 67 years; range, 37-80) were treated with cytarabine (200 mg/m(2)/d) for 5 days followed by (213)Bi-lintuzumab (18.5-46.25 MBq/kg). The MTD of (213)Bi-lintuzumab was 37 MB/kg; myelosuppression lasting >35 days was dose limiting. Extramedullary toxicities were primarily limited to grade ≤2 events, including infusion-related reactions. Transient grade 3/4 liver function abnormalities were seen in five patients (16%). Treatment-related deaths occurred in 2 of 21 (10%) patients who received the MTD. Significant reductions in marrow blasts were seen at all dose levels. The median response duration was 6 months (range, 2-12). Biodistribution and pharmacokinetic studies suggested that saturation of available CD33 sites by (213)Bi-lintuzumab was achieved after partial cytoreduction with cytarabine. Sequential administration of cytarabine and (213)Bi-lintuzumab is tolerable and can produce remissions in patients with AML.