A novel NMDA antagonist, MK-801, impairs performance in a hippocampal-dependent spatial learning task.
N-Methyl-d-aspartate (NMDA) receptors have been implicated with the triggering of long-term potentiation, a currently studied physiological model of learning and memory. The compound (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (MK-801) has recently been classified as a potent and selective NMDA antagonist acting at the associated ion channel. After determination of the highest intraperitoneal dose of MK-801 at which increases in activity (measured in photocell activity cages and 3-arm maze) were not observed (0.2 mg/kg), rats that had been previously trained to obtain food pellets in an 8-arm radial maze up to criterion were tested with 0.1 and 0.2 mg/kg doses. Dose-related decreases in "efficiency" in the task were found. The present findings support the suggestion that NMDA antagonists cause impairments in "working memory" and also support the status of long-term potentiation as a physiological model of memory.


Combination effect of azthreonam with four aminoglycosides on nosocomial gram-positive cocci and non-fermenting gram-negative bacteria.
The inhibitory combination effect of azthreonam with gentamicin, tobramycin, amikacin and netilmicin respectively against 50 non-fermenting gram-negative rods and 30 gram-positive cocci was compared using the checkerboard agar dilution technique. On average 49.5% of all non-fermenting strains were inhibited by additive, and 48.5% by synergistic azthreonam-aminoglycoside combinations, but only 4.5% of the gram-positive cocci were inhibited by synergistic combinations. No antagonism occurred. No significant differences could be found between the effects of the respective azthreonam-aminoglycoside combinations.


Frequent rearrangements of retinoic acid receptor alpha gene and myl gene, and rare mutations of RAS and FMS genes in acute promyelocytic leukemia.
To investigate leukemogenesis of acute promyelocytic leukemia (APL), we studied the involvements of retinoic acid receptor alpha (RAR alpha) and myl genes, and also the frequency of N-RAS, K-RAS, H-RAS, and FMS point mutations in sixteen patients with APL. By Southern blot analysis, the rearrangements of RAR alpha gene were detected in 13 patients (81.2%), and myl gene in 14 (87.5%). Either RAR alpha or myl gene rearrangements were found in all patients including one with normal karyotype. Breakpoints of both genes were clustered. By direct sequencing, no point mutations were found at codons 12, 13, and 61 of N-, K-, and H-RAS genes, and at codons 301 and 969 of FMS gene. These data indicate that myl-RAR alpha translocation occurs frequently in APL, whereas RAS and FMS mutations are rare in APL. It may be suggested that leukemogenesis of APL is different from other subtypes of acute myelogenous leukemia, and multistep leukemogenesis may not be a prevalent feature in APL.


Medical complications in male adolescents with anorexia nervosa.
Medical information on male anorectics is scant. We present data on 10 males with anorexia nervosa, who were treated at our Eating Disorders Center during a twelve-year period. Retrospective chart review. All patients were malnourished weighing 80% or less of their ideal body weight with a mean B.M.I. of 13.5 +/- 2.0. Height below the 50th percentile was evident in 80% of the patients, and was below the 10th percentile in 30% of the patients. Structural brain changes on brain computerized tomography scans were noted in seven out of nine patients and more than 50% had mild anemia relative to the Tanner stage. Other findings included a mean presenting heart rate of 68.3 +/- 17: four out of ten patients had presenting heart rates of 80 or greater and of these, three had serious medical problems and were severely malnourished. Two patients had cardiac complications and one had a life-threatening electrolyte disturbance. Despite the small number of patients, the proportion of male adolescent anorectics with medical abnormalities seems high, and may be due to difficulties in establishing the diagnosis and delay in seeking medical attention. Patients who had heart rates of 80 or greater were perhaps sicker and further along in their development of congestive heart failure, thus explaining their initial relative tachycardia. We suggest a higher index of suspicion for congestive heart failure and closer medical monitoring when a malnourished adolescent with anorexia nervosa presents with relatively elevated heart rates.


Patient experience in a surgical assessment unit following a closed-loop audit using a Kaizen Lean system.
The Acute Surgical Assessment Unit (ASAU) in University Hospital Limerick (UHL) has provided a solution to overcrowding and long waiting times since centralization of emergency services to UHL. Recognising the importance of its evolving role, the ASAU in UHL has recently undergone a major revamp to ease the pressure in the overcrowded emergency department (ED). This included a new purpose state-of-the-art-built unit and equipment, improved staffing levels and use of a Kaizen Lean system to identify key area of delays and inefficiency with subsequent implementation of suggestions derived after Kaizen Lean. Patient satisfaction reporting was analysed in the older building and subsequently in the new site post Kaizen Lean to complete a closed-loop audit. The aim of the study was to examine patient satisfaction response rates with the ASAU prior to and following Kaizen Lean implementation and transfer to a new purpose-built unit. The survey comprised of two phases. In phase 1, 100 questionnaires were distributed to patients in ASAU (older building, pre-Kaizen Lean). In phase 2, the survey was repeated (100 patients) after Kaizen Lean implementation and transfer to the new state-of-the-art unit. Questionnaire design was based on WHO strategy on responsiveness measurement guidelines and was tailored to a population of surgical patients. Results were analysed using IBM SPSS, version 21 and Excel 2013. Two hundred questionnaires were analysed. Implementation of suggestions derived post Kaizen Lean translated into improved resource usage with reduced waiting time to be seen by nurses and doctors. Patients had better awareness about their treatment plan and planned next steps in the management. Satisfaction across different domains, perceptions of privacy and overall treatment were also improved. A Kaizen Lean approach improved the transition of an ASAU to a new purpose-built unit and further improved overall patient satisfaction with services of the ASAU.


Reproductive disorders in dairy cattle under semi-intensive system of rearing in North-Eastern India.
This study was conducted to determine the incidence of major reproductive problems of dairy cattle reared under a semi-intensive system by small and marginal farmers in Meghalaya province of North-Eastern India. In a 3 years study, a total of 576 crossbred dairy cattle (212 Holstein Friesian cross and 364 Jersey cross) from all districts (n=11) of Meghalaya were assessed with the survey, clinical examination, and personal observations. Out of the total animal assessed, 33.85% (n=195) were found to be affected with one or more of the clinical reproductive problems. Repeat breeding (RB), anestrus, retention of fetal membrane, and abortion were found to be the major clinical reproductive problems. Out of the total animal affected with reproductive disorders, the incidence of anestrus, RB, retention of fetal membrane, and abortion was found to be 31.79% (n=62), 24.61% (n=48), 14.35% (n=28), and 11.25% (n=22), respectively. In addition, dystocia (5.12%), prolapse (1.53%), endometritis (4.61%), and pyometra (6.66%) were minor clinical reproductive problems. There was a significant difference in the incidence of reproductive disorders with respect to breed, age, and parity. It was revealed from this study that RB, anestrus, retention of fetal membrane, and dystocia are the major clinical reproductive problems in Meghalaya. Results indicated unsatisfactory feeding, housing, and health management practices are the main cause of low fertility of dairy cows. Lack of scientific knowledge, low access to breeding, and health services further contributed to low productivity and fertility.


Microcirculatory alterations during haemorrhagic shock and after resuscitation in a paediatric animal model.
Haemorrhagic shock is frequent in paediatric trauma patients and after cardiac surgery, especially after cardiopulmonary bypass. It has demonstrated to be related to bad outcome. To evaluate changes on microcirculatory parameters during haemorrhagic shock and resuscitation in a paediatric animal model. To determine correlation between microcirculatory parameters and other variables routinely used in the monitoring of haemorrhagic shock. Experimental study on 17 Maryland pigs. Thirty minutes after haemorrhagic shock induction by controlled bleed animals were randomly assigned to three treatment groups receiving 0.9% normal saline, 5% albumin with 3% hypertonic saline, or 5% albumin with 3% hypertonic saline plus a bolus of terlipressin. Changes on microcirculation (perfused vessel density (PVD), microvascular blood flow (MFI) and heterogeneity index (HI)) were evaluated and compared with changes on macrocirculation and tisular perfusion parameters. Shock altered microcirculation: PVD decreased from 13.5 to 12.3 mm mm(-2) (p=0.05), MFI decreased from 2.7 to 1.9 (p<0.001) and HI increased from 0.2 to 0.5 (p<0.001). After treatment, microcirculatory parameters returned to baseline (PVD 13.6 mm mm(-2) (p<0.05), MFI 2.6 (p<0.001) and HI 0.3 (p<0.05)). Microcirculatory parameters showed moderate correlation with other parameters of tissue perfusion. There were no differences between treatments. Haemorrhagic shock causes important microcirculatory alterations, which are reversed after treatment. Microcirculation should be assessed during haemorrhagic shock providing additional information to guide resuscitation.


The mechanism of the calcium signal and correlation with histamine release in 2H3 cells.
Rat basophil leukemic (2H3) cells ( Siraganian , R.P., McGivney , A., Barsumian , E. L., Crews, F. T., Hirata , F., and Axelrod , J. (1982) Fed. Proc. 41, 30-34) loaded with fluorescent Ca2+ indicator quin 2 ( Tsien , R. Y. (1980) Biochemistry 19, 2396-2404) showed a rapid increase in free cytosol calcium concentration [( Ca]i) when histamine release was induced. Intracellular quin 2 concentrations up to 7 mM did not affect release of histamine in response to antigen (aggregated ovalbumin) or concanavalin A with cells primed with antigen-specific monoclonal IgE, or in response to Ca2+ ionophores. The [Ca]i increased from approximately 105 nM to a maximum of approximately 1200 nM within 2 to 3 min after antigenic stimulation and then declined slowly over 30 min toward the level in unstimulated cells. Histamine release was most rapid as [Ca]i reached the maximum value and then decreased continuously with [Ca]i over the subsequent 30 min. Neither the Ca signal nor histamine release was observed when the Ca2+ concentration in the medium [( Ca]o) was less than 50 microM, but both responses were restored on readdition of Ca2+ to 1 mM. The maximal Ca signal was obtained when [Ca]o was approximately greater than 1 mM and was half-maximal at [Ca]o congruent to 0.4 mM. In marked contrast [Ca]i in unstimulated cells varied very little with [Ca]o from 0.1 to 1 mM. Maintenance of the Ca signal required the continuous presence of stimulating ligand, external Ca2+, and the maintenance of cellular ATP; metabolic inhibitors blocked or reversed the Ca signal. La+ ions also caused a rapid and reversible block of the Ca signal and histamine release. The data are interpreted in a model in which the Ca signal is generated by a La3+-sensitive signal influx pathway that is functionally independent of the normal Ca2+ influx pathway in unstimulated cells, and that allows a 10-fold or greater increase in rate of Ca2+ entry. The Ca signal is maintained dynamically by the balance between the increased Ca2+ influx and active Ca2+ efflux across the plasma membrane.


Comparative interaction of free and liposome-encapsulated nor-muramyl dipeptide or muramyl tripeptide phosphatidylethanolamine (3H-labelled) with human blood monocytes.
The purpose of this study was to analyse on biochemical and functional levels the interaction of free and liposome-encapsulated nor-muramyl dipeptide (nor-MDP) or muramyl tripeptide phosphatidylethanolamine (MTP-PE) with human peripheral blood monocytes. The activation of tumoricidal properties in monocytes by free MTP-PE required approximately 40-fold less material than free nor-MDP. Encapsulation of either MTP-PE or nor-MDP within multilamellar liposomes (MLV) increased the efficiency of the immunomodulators for activation of monocytes. The initial interaction of free 3H-nor-MDP or 3H-MTP-PE with monocytes was influenced by lipophilic derivatization, but neither derivatives exhibited characteristics of specific binding to the monocyte surface. The encapsulation of 3H-nor-MDP or 3H-MTP-PE within MLV increased uptake of both compounds by monocytes. The metabolic fate of MLV-entrapped 3H-nor-MDP was unaltered, but liposome encapsulation retarded the metabolism of 3H-MTP-PE. Collectively, the data suggest that the activation of monocytes by muramyl peptides results from an intracellular interaction which can be modulated by both lipophilic derivatization and/or liposome-encapsulation of this immunomodulator.


Enantiomeric separations of binaphthyl derivatives by capillary electrophoresis using N-(2-hydroxydodecyl)-L-threonine as chiral selector: effect of organic additives.
The chiral selectivity of a novel amphiphile, N-(2-hydroxydodecyl)-L-threonine (2-HDT), was evaluated for enantiomeric resolution of three binaphthyl derivatives (+/-)-1,1'-bi-2-naphthol, (+/-)-1,1'-binaphthyl-2,2'-diamine, and (+/-)-1,1'-binaphthyl-2,2'-diylhdrogen phosphate (BNP) by micellar EKC. The effects of three organic modifiers, methanol, isopropanol, and acetonitrile, on the separations of enantiomers of these compounds were investigated. Separation of enantiomers could be achieved in relatively dilute solutions of the pure surfactant. However, best separations of enantiomers were obtained only in the presence of 10% v/v acetonitrile. Enantiomeric impurity in nonracemic mixtures of R- and S-forms of BNP was determined.


New coumarin-based anti-inflammatory drug: putative antagonist of the integrins alphaLbeta2 and alphaMbeta2.
This study was conducted to investigate putative antagonism of integrin receptors alphaMbeta2 and alphaLbeta2 by a novel coumarin derivative (BOL-303225-A), its efficacy in-vivo after retinal ischaemia-reperfusion injury, and its bioavailability in rat plasma. A cellular adhesion assay in Jurkat and U937 cells, and a flow cytometry assay with an antibody against the beta2 subunit were conducted. BOL-303225-A bioavailability in rat plasma and the retinal levels of myeloperoxidase (MPO) after ischaemia-reperfusion injury were evaluated after oral administration (10 mg kg(-1)). In-vitro cell viability assays revealed no cytotoxicity for BOL-303225-A over a wide dose range, and IC50 values of 32.3 +/- 1.5 muM and 84.95 +/- 2.3 muM were found for Jurkat and U937 cells, respectively. The drug showed specific binding to the alphaMbeta2 and alphaLbeta2 integrin receptors expressed by U937 and Jurkat cells, respectively, producing a fluorescence shift towards lower values in a concentration-dependent manner. The pharmacokinetic profile of BOL-303225-A exhibited rapid absorption following oral administration in the rat. A significant reduction of retinal MPO levels was observed in drug-treated rats. This study demonstrated that BOL-303225-A acts as an antagonist of the integrin alphaLbeta2 and alphaMbeta2 receptors, suggesting that this drug could be used for ocular diseases such as diabetic retinopathy.


Solubilization of the membrane bound lactose specific component of the staphylococcal PEP dependant phosphotransferase system.
The membrane bound lactose specific component of the PEP dependant phosphotransferase system of Staphylococcus aureus has been solubilized using the non ionic detergent Triton X-100. Some properties of the crude soluble enzyme are reported.


Autumnal leaf conductance and apparent photosynthesis by saplings and sprouts in a recently disturbed northern hardwood forest.
Leaf surface conductance and apparent photosynthesis were measured during late summer and autumn on saplings and sprouts of pin cherry (Prunus pensylvanica), yellow birch (Betula alleghaniensis), American beech (Fagus grandifolia), and sugar maple (Acer saccharum) naturally revegetating a site in the northern hardwood forest 5 years following a commercial whole-tree harvest. Prior to the disturbance (i.e., the harvest) the site was codominated by American beech, sugar maple, and yellow birch, whereas after the disturbance pin cherry was the dominant species. Conductance and photosynthetic rate of pin cherry leaves were comparatively high while those of American beech and sugar maple were low. Pin cherry retained green, physiologically active leaves longer into autumn than American beech and sugar maple. The rates and seasonal duration of leaf gas exchange on the disturbed site were therefore greater than they would have been had the site not become dominated by pin cherry.


An atypical presentation of Crohn disease in the elderly. A case report and Literature review.
The Authors present a case of an insidious onset of Crohn Disease (CD) in an elderly patient. Diagnosis complicated by extraintestinal manifestation properly of old age could be delayed and often made after surgery on the histological specimen as in our case. CD is uncommon as primary manifestation in old age, often unsuspected, incorrectly diagnosed and in many case the clinical features may lead to late diagnosis. Differential diagnosis of CD in elder people with fever, diarrhoea and abdominal pain is difficult and other symptoms affecting intestinal tract can closely mimic CD symptoms, although the pattern of clinical presentation in older patient resemble those in younger.


Neural crest cells: temperature-dependent transformation by Rous sarcoma virus.
Cranial neural crest cells from chick embryos, when cultured under appropriate conditions, differentiate after approx. 1 week into pigmented cells. Neurol crest cells were infested with a mutant (RSV-BH-Ta) of the Bryan 'high titer' strain of Rous sarcoma virus on the second day of culture before the cells were morphologically differentiated, or later after they became pigmented. Cells infected and maintained at the temperature permissive for transformation (37 degrees C) proliferated rapidly compared to uninfected cells are produced extensive cytoplasmic vacuoles in a fashion similar to other types of cells transformed with RSV-BH-Ta at 37 degrees C. Cells infected and maintained at the non-permissive temperature for transformation (41 degrees C) also proliferated rapidly but did not become morphologically transformed. Transformation occurred reversibly following a shift of temperature. Infection of morphologically undifferentiated neural crest cells at either temperature prevented their differentiation into pigment cells, and infection of pigmented neural crest cells at either temperature led to a gradual loss of pigmentation. These results suggest that even at the non-permissive temperature the virus may regulate the state of differentiation of certain types of cells.


Chronic hypoxia-hypercapnia influences cognitive function: a possible new model of cognitive dysfunction in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is a slowly progressive lung disease that results in several complications, including cognitive dysfunction. Some evidences support that cognitive impairment is common and clinically important in COPD, but the exact mechanism is still unclear. It has been confirmed that chronic hypoxia-hypercapnia contributes a lot to the development in pathophysiology of COPD. Data from some pilot studies indicated that chronic hypoxia-hypercapnia influences cognitive functions both in patients and in animals, which includes some distinctive pattern of cognitive dysfunction in human being or impairment of spatial learning-memory in rat. Therefore, we propose that cognitive impairment is strongly related to combination of chronic hypoxia and hypercapnia, and chronic hypoxia-hypercapnia-induced animal models may mimic the cognitive dysfunction of COPD. Attempts to confirm this hypothesis may lead to new model of cognitive dysfunction in COPD.


Reversed-phase liquid chromatography of elastin peptides.
Soluble fragments of elastin are frequently present in biological tissue in small amounts. Because of their hydrophobic character, these peptides are not well resolved by a number of conventional techniques. However, their separation should be possible by reversed-phase chromatography. A wide range of columns, gradients and solvents were evaluated. Two systems are described. One was a C18 liganded silica column eluted isocratically by gravity flow. Some degree of size fractionation was achieved with larger peptides being eluted with methanol and smaller ones with isopropanol. The second system uses a pressurized elution from another C18 ligand column. A concave gradient of trifluoroacetic acid-acetonitrile with a decreasing acetonitrile concentration was optimal. Similar resolution of peptides produced by a variety of digestion methods was obtained with the lower-molecular-mass peptides eluting in the middle of the gradient.


Invasive v non-invasive assessment of the carotid arteries prior to trans-sphenoidal surgery.
Imaging studies in 47 patients who were to undergo trans-sphenoidal surgery were analysed with reference to the vascular structures in the parasellar region. The results of cavernous sinography, dynamic contrast enhanced Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) showed good correlation with each other and with the appearances found at operation. CT and MRI, both non-invasive investigations, are therefore reliable preliminary screening methods for identifying the small proportion of patients on whom other imaging techniques need to be performed.


Dose escalation biodistribution, positron emission tomography/computed tomography imaging and dosimetry of a highly specific radionuclide-labeled non-blocking nanobody.
Immunotherapy is a valuable option for cancer treatment, and the curative effect of anti-PD-1/PD-L1 therapy correlates closely with PD-L1 expression levels. Positron emission tomography (PET) imaging of PD-L1 expression is feasible using 68Ga-NOTA-Nb109 nanobody. 68Ga-NOTA-Nb109 was generated by radionuclide (68Ga) labeling of Nb109 using a NOTA chelator. To facilitate clinical trials, we explored the optimal dose range of 68Ga-NOTA-Nb109 in BALB/c A375-hPD-L1 tumor-burdened nude mice and C57-hPD-L1 transgenic MC38-hPD-L1 tumor-burdened mice by administration of a single intravenous dose of 68Ga-NOTA-Nb109 and confirmed the dose in cynomolgus monkeys. The biodistribution data of cynomolgus monkey PET images were extrapolated to estimate the radiation dose for the adult male and female using OLINDA2.1 software. 68Ga-NOTA-Nb109 was stable in physiologic media and human serum. Ex vivo biodistribution studies showed rapid and specific uptake in A375-hPD-L1 or MC38-hPD-L1 tumors. The estimated ED50 was approximately 5.4 µg in humanized mice. The injected mass (0.3-100 µg in nude mice and approximately 1-100 µg in humanized mice) greatly influenced the general biodistribution, with a better tumor-to-background ratio acquired at lower doses of Nb109 (0.3-10 µg in nude mice and approximately 1 µg in humanized mice), indicating maximum uptake in tumors at administered mass doses below the estimated ED50. Therefore, a single 15-μg/kg dose was adopted for the PET/CT imaging in the cynomolgus monkey. The highest specific and persistent uptake of the tracer was detected in the spleen, except the levels in the kidney and urine bladder, which was related to metabolism and excretion. The spleen-to-muscle ratio of the tracer exceeded 10 from immediately to 4 h after administration, indicating that the dose was appropriate. The estimated effective dose was calculated to yield a radiation dose of 4.1 mSv to a patient after injecting 185 MBq of 68Ga-NOTA-Nb109. 68Ga-NOTA-Nb109 showed specific accumulation in hPD-L1 xenografts in ex vivo biodistribution studies and monkey PET/CT imaging. The dose escalation distribution data provided a recommended dose range for further use, and the safety of the tracer was confirmed in dosimetry studies.


Patient information, communication and competence empowerment in oncology: Results and learnings from the PIKKO study.
Many concepts for accompanying and supporting cancer patients exist and have been studied over time. One of them was PIKKO (a German acronym for "Patient information, communication and competence empowerment in oncology"), which combined a patient navigator, socio-legal and psychological counseling (with psychooncologists), courses dealing with various supportive aspects, and a knowledge database with validated and easy-to-understand disease-related information. The aim was to increase the patients' health-related quality of life (HRQoL), self-efficacy as well as health literacy and to reduce psychological complaints such as depression and anxiety. To this purpose, an intervention group was given full access to the modules in addition to treatment as usual, while a control group received only treatment as usual. Over twelve months, each group was surveyed up to five times. Measurements were taken using the SF12, PHQ-9, GAD, GSE, and HLS-EU-Q47. No significant differences were found in scores on the mentioned metrics. However, each module was used many times and rated positively by the patients. Further analyses showed a tendency higher score in health literacy with higher intensity of use of the database and higher score in mental HRQoL with higher intensity of use of counseling. The study was affected by several limitations. A lack of randomization, difficulties in recruiting the control group, a heterogeneous sample, and the COVID-19 lockdown influenced the results. Nevertheless, the results show that the PIKKO support was appreciated by the patients and the lack of measurable effects was rather due to the mentioned limitations than to the PIKKO intervention. This study was retrospectively registered in the German Clinical Trial Register under DRKS00016703 (21.02.2019, retrospectively registered). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016703.


Amyloid structures: much more than just a cross-β fold.
In recent years our understanding of amyloid structure has been revolutionised by innovations in cryo-electron microscopy, electron diffraction and solid-state NMR. These techniques have yielded high-resolution structures of fibrils isolated from patients with neurodegenerative disease, as well as those formed from amyloidogenic proteins in vitro. The results not only show the expected cross-β amyloid structure, but also reveal that the amyloid fold is unexpectedly diverse and complex. Here, we discuss this diversity, highlighting dynamic regions, ligand binding motifs, cavities, non-protein components, and structural polymorphism. Collectively, these variations combine to allow the generic amyloid fold to be realised in three dimensions in different ways, and this diversity may be related to the roles of fibrils in disease.


The essential role of Ca2+ in the activity of bovine pancreatic deoxyribonuclease.
DNase requires Ca2+ for activity against DNA with Mg2+. The Ca2+ selective chelating agent, ethylene glycol bis(beta-aminoethyl ether)-N, N'-tetraacetic acid, (EGTA) inhibits DNase completely at pH 7 or 8, and subsequent addition of excess Ca2+ reverses inhibition in less than one second. DNase action can be stopped at any point by the addition of excess EGTA over Ca2+. Ca2+ is required for DNase to bind substrate. Gel filtration experiments fail to show DNase binding to 0.2 mg per ml of DNA at 5 mm Mg2+ and 10-4 M EGTA. The concentration of Ca2+ needed for half of maximum DNase activity decreases with increases DNA concentration, from 1.2 times 10-5 M Ca2+ at 2.3 times 10-5 M DNA-P to about 4 times 10-7 M Ca2+ at 2.3 DNA-P. Kinetic analysis by the titrametic assay of protons releases shows that V max is independent of Ca2+ concentration while Km increases from 7.7 times 10-5 M DNA-P at 5 times 10-4 M Ca2+ to 3.4 times 10-4 M DNA-P at 5 times 10-6 M Ca2+. Both of these results are predicted by a rate equation which is derived from the assumption that DNase must bind Ca2+ before it can bind DNA. The essential Ca2+ atom probably binds to the one of two high affinity Ca2+ binding sites on DNase which cannont bind Mg2+ or Mn2+. The only other divalent metal ions which can bind to this site, Sr2+ and Ba2+, are also the only metal ions which can substitute for Ca2+ in DNase action against DNA with Mg2+. Some DNase activity is obtained in the absence of added Ca2+ with Mg2+ at pH 6 or below and with Mn2+ or Co2+ at pH 8. These assay solutions are contaminated by 1 to 3 muM Ca2+, which may be sufficient to account for the observed activity.


Amisulpride: efficacy in the management of chronic patients with predominant negative symptoms of schizophrenia.
Amisulpride is a dopamine D2/D3-selective antipsychotic drug with potent antipsychotic efficacy in acute exacerbations of schizophrenia. It also possesses substantial efficacy in chronic schizophrenic patients with enduring predominant negative symptoms. This unique property has been demonstrated in a series of short (6 weeks) and medium-/long-term (6-12 months) double-blind placebo-controlled studies. The patients in these studies were carefully selected and assessed to avoid confounding results with non-specific changes in other symptom domains. The results not only show effects on negative symptoms at the optimal dose of 100 mg/day, but also significant improvement in global functioning. The effect observed in short-term studies was maintained over longer treatment periods (6-12 months). Amisulpride was well tolerated with a safety profile similar to placebo. These results open a new therapeutic approach for negative symptoms, one of the most disabling aspects of schizophrenia.


Three-unit fixed dental prostheses supported by either two abutment implants or two abutment teeth: A comparative retrospective cohort study.
In general, similar restorative constructions are made on natural teeth and on dental implants. The assumption is made that implants and their restoration perform the same as natural roots and their prosthetic restoration. Evaluating cohorts of three-unit bridges on teeth and on implants, this retrospective clinical study aimed to compare implants and teeth as supporting units, including the reconstructions, in terms of survival, success, clinical, radiographic, and patient-reported outcomes. From an 8-year period, all patients treated with a posterior three-unit fixed reconstruction on either implants or teeth, with a follow-up of at least 2 years, were identified. For each implant-supported reconstruction, a comparable tooth-supported reconstruction was selected, based on the length of follow-up, the material of the reconstruction, and the location in either the maxilla or mandible. For the Implant-group, 24 patients could be matched with 24 best matching patients with tooth-supported fixed dental prostheses (FPDs). Supporting implants and implant-supported reconstructions were all in function with a mean follow-up of 52 ± 23 months. Two tooth-supported reconstructions had been replaced (91.7% survival) (mean follow-up: 52 ± 19 months). Radiographic bone levels and soft tissue conditions were favorable in both groups with minor differences. There was no significant difference in overall patient satisfaction. The modified USPHS-score revealed an 87.5% overall success in the Implant-group and 91.7% in the Tooth-group. Implant-supported three-unit FDPs are a reliable treatment option with survival and success rates not significantly different from the results of tooth-supported three-unit FDPs.


Realism and constructivism in social perception.
Jussim's critique of social psychology's embrace of error and bias is needed and often persuasive. In opting for perceptual realism over social constructivism, however, he seems to ignore a third choice - a cognitive constructivism which has a long and distinguished history in the study of nonsocial perception, and which enables us to understand both accuracy and error.


The Role of Viruses in Identifying and Analyzing RNA Silencing.
Adaptive antiviral immunity in plants is an RNA-based mechanism in which small RNAs derived from both strands of the viral RNA are guides for an Argonaute (AGO) nuclease. The primed AGO specifically targets and silences the viral RNA. In plants this system has diversified to involve mobile small interfering RNAs (siRNAs), an amplification system involving secondary siRNAs and targeting mechanisms involving DNA methylation. Most, if not all, plant viruses encode multifunctional proteins that are suppressors of RNA silencing that may also influence the innate immune system and fine-tune the virus-host interaction. Animal viruses similarly trigger RNA silencing, although it may be masked in differentiated cells by the interferon system and by the action of the virus-encoded suppressor proteins. There is huge potential for RNA silencing to combat viral disease in crops, farm animals, and people, although there are complications associated with the various strategies for siRNA delivery including transgenesis. Alternative approaches could include using breeding or small molecule treatment to enhance the inherent antiviral capacity of infected cells.


Paced QT interval is a better predictor of mortality than the intrinsic QT interval: long-term follow-up study.
Prolongation of the corrected QT (QTc) interval on 12-lead electrocardiogram is related to total mortality and sudden cardiac death. The value of the paced QTc interval in predicting mortality has not been investigated. To evaluate the relationship between the paced QTc interval and mortality. Of 1440 patients who underwent pacemaker implantation from January 1990 to March 2010, 766 had a recorded intrinsic and ventricular paced rhythm and were included in this study. The intrinsic and paced QTc intervals were measured on 12-lead electrocardiogram before and 1-month after implantation. During a mean follow-up period of 7 ± 5 years, 189 (24.4%) patients died, of which 63 (8.1%) were cardiac deaths. Compared with patients in the first tertile of the paced QTc interval (<484 ms), patients in the third tertile (>511 ms) were significantly more likely to die (19% vs 29%; P < .05). A comparison of the third and first tertiles of the QTc interval showed that a prolonged paced QTc interval was a significant independent predictor of all-cause mortality (adjusted hazard ratio 2.08; 95% confidence interval 1.44-3.01; P < .001) and cardiac mortality (adjusted hazard ratio 2.53; 95% confidence interval 1.29-4.95; P = .007) and a better predictor than was a prolonged intrinsic QTc interval. When treated as a continuous variable, a prolonged paced QTc interval predicted increased total mortality and cardiac mortality. The paced QTc interval appears to be a more useful marker in predicting bad prognosis than does the intrinsic QTc interval in patients with indications for a permanent pacemaker.


Factors influencing the synthesis of monoester and diester from polyethylene glycol400 and oleic acid by lipase.
Factors influencing the synthesis of mono- and diester of polyethylene glycol400 (PEG400) oleate with immobilized lipase from Candida sp.1619 as biocatalyst were investigated. Mono- and diester were formed with different molar ratios of the substrates after reacting for 6 hours. The amount of monoester to diester formed was in the range of 3.5:1 to 4.1:1 when the molar ratio of acid to PEG400 was 0.25:1 to 2:1. Almost equal amounts of mono- and diesters were produced when the molar ratio of acid to PEG400 was 3:1 to 8:1. When the equilibrium of reaction was reached (22 hours), only diester was found in the reaction mixture with different molar ratio of substrates. The amount of monoester to diester was 1:3.2 in the reaction system containing hexane, even the molar ratio of acid to PEG400 was 2:1.


The Geography of Employment Outcomes for Radiation Oncology Graduates in 2019.
The geographic distribution of practicing radiation oncologists is of concern for multiple stakeholders within the field. Employment outcomes of graduating residents can affect that distribution, and they are of major concern to current residents. Data investigating employment outcomes of recent graduates are sparse. We aimed to analyze the employment outcomes of the radiation oncology residency class of 2019. Using publicly available information, we identified the employment of 179 of 183 graduating residents in the class of 2019. For each, the place of employment, residency program, and medical school were geocoded using Google Maps. We used the rural-urban continuum code (RUCC) published by the United States Department of Agriculture to determine the rurality of each location and compared employment outcomes by RUCC and program size. Two thirds of graduates (66%) took a position in a county within a metropolitan area with a population greater than 1,000,000 people; only 3.4% took a position in a county outside of a metropolitan area. Graduates of smaller programs (≤6 residents) and those in smaller metropolitan areas were more likely to take positions in smaller metropolitan areas or nonmetropolitan areas. The geographic distance between location of employment and residency program did not significantly vary by program size or size of metropolitan area where a residency program was located. Among the class of 2019, a small proportion took positions in nonmetropolitan areas. Smaller programs and those in smaller metropolitan areas may be more likely to produce graduates that practice in similar settings, but those graduates might not do so locally. We advocate for a centralized, prospective data collection of employment outcomes for graduating residents to refine these analyses and to reduce employment prospect information asymmetry for trainees.


Prevalence, management and clinical challenges associated with acute faecal incontinence in the ICU and critical care settings: the FIRST cross-sectional descriptive survey.
To evaluate the prevalence, awareness and management of acute faecal incontinence with diarrhoea (AFId) in the Intensive Care Unit. Cross-sectional descriptive survey design of intensive care units across Germany, Italy, Spain and the United Kingdom. 962 questionnaires were completed by nurses (60%), physicians (29%) and pharmacists or purchasing personnel (11%). The estimated prevalence of AFId ranged from 9 to 37% of patients on the day of the survey. The majority of respondents reported a low-moderate awareness of the clinical challenges associated with AFId. Patients with AFId commonly had compromised skin integrity, which included perineal dermatitis, moisture lesions or sacral pressure ulcers. Reducing the risk of cross-infection and protecting skin integrity were rated as the most important clinical challenges. 49% had no hospital protocol or guideline for AFId management. There was also a low awareness of nursing time spent managing AFId; 60% of respondents estimated that 10-20 minutes are required for managing an AFId episode by 2-3 healthcare staff. AFId in the critical care setting may be an underestimated problem which is associated with a high use of nursing time.


IgG index of cerebrospinal fluid can reflect pathophysiology associated with Lewy bodies in Parkinson's disease.
Neuroinflammation is one of the pathophysiologies of Parkinson's disease (PD). Lewy bodies, the pathological hallmark of PD, emerge as a consequence of α-synuclein aggregation, and neuroinflammation is induced concurrently with this aggregation. Imaging and cerebrospinal fluid (CSF) biomarkers that reflect PD pathophysiology have been developed or are under investigation. The IgG index of CSF is a marker of inflammation, and may also reflect the pathophysiology of PD. We examined if the IgG index reflects the pathophysiology of PD in drug-naïve PD patients. The subjects were 20 consecutive PD patients who underwent 123I-MIBG scintigraphy for assessment of the heart to mediastinum (H/M) ratio and wash out rate, 123I-Ioflupane SPECT for examination of the specific binding ratio in the striatum, and lumbar puncture before treatment. The CSF IgG index and levels of pathogenic proteins (total α-synuclein, oligomeric α-synuclein, total tau, phosphorylated tau and amyloid Aβ1-42) were determined. The IgG index was compared with the other parameters using Spearman correlation analysis. The IgG index showed a significant correlation with the H/M ratio in early (r = -0.563, p = 0.010) and delayed (r = -0.466, p = 0.038) images in 123I-MIBG scintigraphy and with the CSF total tau level (r = -0.513, p = 0.021). Neuroinflammation is involved in PD pathophysiology in some patients, and a higher IgG index indicates the presence of neuroinflammation accompanied by emergence of Lewy bodies.


Differential assay and biological significance of poly(ADP-ribose) polymerase activity in isolated liver nuclei.
Poly(ADP-ribosyl)ation of nuclear proteins is catalyzed by poly(ADP-ribose) polymerase. This enzyme is involved in the regulation of basic cellular functions of DNA metabolism. DNA breaks induced by DNA-damaging agents trigger the activation of poly(ADP-ribose) polymerase increasing its endogenous level. This increase modifies the pattern of poly(ADP-ribosyl)ated chromatin proteins. In this paper we describe a procedure for the isolation of intact nuclei from rat liver to be used for the endogenous activity assay. Artifactual activation of the enzyme was avoided since a very low level of DNA-strand breaks occurs during the isolation of nuclei. We present a series of experiments which prove the ability of this procedure to detect increases in endogenous liver activity without modification of the total level. The application of this technique can be useful for a better understanding of the role of early changes in poly(ADP-ribose) polymerase level in physiological conditions and during exposure to DNA-damaging agents.


On the road to bioremediation of "dioxin".
Mohammadi and Sylvestre report engineering of a dioxygenase to create an enzyme that attacks dibenzofuran in the lateral position. Subsequent oxidation and a second dioxygenation produced ring-open products. All metabolites were unambiguously identified by 1H-NMR. This new pathway targets degradation of chlorinated dibenzofurans.


MRI findings of chronic distal tendon biceps reconstruction and associated post-operative findings.
Rupture of the distal biceps tendon is becoming increasingly diagnosed due to an active aging population and an increase in diagnostic imaging opportunities. While physical exam may help in diagnosis, magnetic resonance imaging (MRI) is particularly useful in evaluating chronic rupture. Although partial tears can be managed conservatively, the gold standard treatment for a chronic distal biceps tear is anatomic reinsertion with additional use of an allograft or autograft. No study has highlighted the normal appearance and postsurgical complications seen on MRI associated with allograft or autograft usage. Clinicians and radiologists may be unaware of the normal and abnormal post-operative imaging findings and their clinical relevance. The purpose of this manuscript is to discuss the epidemiology, clinical presentation, and preoperative MRI findings of distal biceps ruptures necessitating reconstruction, to explain distal biceps tendon surgical reconstruction technique with allograft or autograft usage, to display the normal and abnormal post-operative MRI findings, and to review the clinical outcomes associated with the procedure.


Progestin Primed Ovarian Stimulation (PPOS) protocol yields lower euploidy rate in older patients undergoing IVF.
To explore if exogenous progestin required for progestin primed ovarian stimulation (PPOS) protocol compromises the euploidy rate of patients who underwent preimplantation genetic testing cycles when compared to those who received the conventional gonadotropin-releasing hormone (GnRH) antagonist protocol. This retrospective cohort study analyzed 128 preimplantation genetic testing for aneuploidy (PGT-A) cycles performed from January 2018 to December 2021 in a single university hospital-affiliated fertility center. Infertile women aged 27 to 45 years old requiring PGT-A underwent either PPOS protocol or GnRH-antagonist protocol with in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for fertilization. Frozen embryo transfers were performed following each PGT-A cycle. Data regarding the two groups were analyzed using the Statistical Package for Social Sciences (SPSS) version 22.0 (SPSS Inc., Chicago, IL). Patients who underwent PPOS treatment had significantly reduced blastocyst formation rate and euploidy rate compared to those who received the GnRH antagonist protocol. Subgroup-analysis was performed by stratifying patients' age into elder and young subgroups (elder: ≥ 38-year-old, young: < 38-year-old). In the elder sub-population, the blastocyst formation rate of the PPOS group was significantly lower than that of the GnRH-antagonist group (45.8 ± 6.1% vs. 59.9 ± 3.8%, p = 0.036). Moreover, the euploidy rate of the PPOS group was only about 20% of that of the GnRH-antagonist group (5.4% and 26.7%, p = 0.006). In contrast, no significant differences in blastocyst formation rate (63.5 ± 5.7% vs. 67.1 ± 3.2%, p = 0.45) or euploidy rate (30.1% vs. 38.5%, p = 0.221) were observed in the young sub-population. Secondary outcomes, which included implantation rate, biochemical pregnancy rate, clinical pregnancy rate, live birth rate, and miscarriage rate, were comparable between the two treatment groups, regardless of age. When compared to the conventional GnRH-antagonist approach, PPOS protocol could potentially reduce the euploidy rate in aging IVF patients. However, due to the retrospective nature of this study, the results are to be interpreted with caution. Before the PPOS protocol is widely implemented, further studies exploring its efficacy in larger populations are needed to define the optimal patient selection suitable for this method. Human Investigation and Ethical Committee of Chang Gung Medical Foundation (202200194B0).


Impact of Duodenal-Jejunal Exclusion on Satiety Hormones.
Bariatric procedures that exclude the proximal small intestine lead to significant weight loss which is probably mediated by changes in hormones that alter appetite, such as peptide YY (PYY), ghrelin, cholecystokinin (CCK), and leptin. Here, the effect of the non-surgical duodenal-jejunal bypass liner (DJBL) on concentrations of hormones implicated in appetite control was investigated. A two-center prospective study was conducted between January and December 2010. Seventeen obese subjects with type 2 diabetes were treated with the DJBL for 24 weeks. Fasting concentrations of leptin and meal responses of plasma PYY, CCK, and ghrelin were determined prior to and after implantation of the DJBL. At baseline, subjects had an average body weight of 116.0 ± 5.8 kg. One week after implantation, subjects had lost 4.3 ± 0.6 kg (p < 0.01), which progressed to 12.7 ± 1.3 kg at week 24 (p < 0.01). Postprandial concentrations of PYY and ghrelin increased (baseline vs. week 1 vs. week 24 PYY: 2.6 ± 0.2 vs. 4.1 ± 0.4 vs. 4.1 ± 0.7 nmol/L/min and ghrelin: 7.8 ± 1.8 vs. 11.0 ± 1.8 vs. 10.6 ± 1.8 ng/mL/min, all p < 0.05). In parallel, the CCK response decreased (baseline vs. week 1 vs. week 24: 434 ± 51 vs. 229 ± 52 vs. 256 ± 51 pmol/L/min, p < 0.01). Fasting leptin concentrations also decreased (baseline vs. week 24: 98 ± 17 vs. 53 ± 10 ng/mL, p < 0.01). DJBL treatment induces weight loss paralleled by changes in concentrations of hormones involved in appetite control.


Assessment and site-specific manipulation of DNA (hydroxy-)methylation during mouse corticogenesis.
Dynamic changes in DNA (hydroxy-)methylation are fundamental for stem cell differentiation. However, the signature of these epigenetic marks in specific cell types during corticogenesis is unknown. Moreover, site-specific manipulation of cytosine modifications is needed to reveal the significance and function of these changes. Here, we report the first assessment of (hydroxy-)methylation in neural stem cells, neurogenic progenitors, and newborn neurons during mammalian corticogenesis. We found that gain in hydroxymethylation and loss in methylation occur sequentially at specific cellular transitions during neurogenic commitment. We also found that these changes predominantly occur within enhancers of neurogenic genes up-regulated during neurogenesis and target of pioneer transcription factors. We further optimized the use of dCas9-Tet1 manipulation of (hydroxy-)methylation, locus-specifically, in vivo, showing the biological relevance of our observations for Dchs1, a regulator of corticogenesis involved in developmental malformations and cognitive impairment. Together, our data reveal the dynamics of cytosine modifications in lineage-related cell types, whereby methylation is reduced and hydroxymethylation gained during the neurogenic lineage concurrently with up-regulation of pioneer transcription factors and activation of enhancers for neurogenic genes.


The application of somatic CRISPR-Cas9 to conditional genome editing in Caenorhabditis elegans.
Forward and reverse genetic approaches have been well developed in the nematode Caenorhabditis elegans; however, efficient genetic tools to generate conditional gene mutations are still in high demand. Recently, the Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR-Cas9) system for genome modification has provided an additional tool for C. elegans researchers to achieve simple and efficient conditional targeted mutagenesis. Here, we review recent advances in the somatic expression of Cas9 endonuclease for conditional gene editing. We present some practical considerations for improving the efficiency and reducing the off-target effects of somatic CRISPR-Cas9 and highlight a strategy to analyze somatic mutation at single-cell resolution. Finally, we outline future applications and consider challenges for this emerging genome editing platform that will need to be addressed in the future.


Combining atomic force microscopy and fluorescence-based techniques to explore mechanical properties of naive and ischemia-affected brain regions in mice.
Knowledge of the brain's structure and function is essential for understanding processes in health and disease. Histochemical and fluorescence-based techniques have proven beneficial in characterizing brain regions and cellular compositions in pre-clinical research. Atomic force microscopy (AFM) has been introduced for mechanical tissue characterization, which may also help investigate pathophysiological aspects in disease-related models such as stroke. While combining AFM and fluorescence-based techniques, this study explored the mechanical properties of naive and ischemic brain regions in mice. Ischemia-affected regions were identified by the green signal of fluorescein isothiocyanate-conjugated albumin. A semi-automated protocol based on a brain atlas allowed regional allocations to the neocortex, striatum, thalamus, hypothalamus, hippocampus, and fiber tracts. Although AFM led to varying measurements, intra-individual analyses indicated a gradually increased tissue stiffness in the neocortex compared to subcortical areas, i.e., the striatum and fiber tracts. Regions affected by ischemia predominantly exhibited an increased tissue stiffness compared to those of the contra-lateral hemisphere, which might be related to cellular swelling. This study indicated intra-individual differences in mechanical properties among naive and ischemia-affected brain regions. The combination of AFM, semi-automated regional allocations, and fluorescence-based techniques thus qualifies for mechanical characterizations of the healthy and disease-affected brain in pre-clinical research.


Effects of soil surface electrochemical properties on soil detachment regulated by soil types and plants.
Soil surface electrochemical properties play an important role in soil detachment. However, the effects of soil surface electrochemical properties on soil detachment have received little attention. This study selected three typical soil types (sandy loam, silt loam and silt clay loam) and two typical herbaceous plants (Stipa bungeana Trin. and Artemisia gmelinii Web. ex Stechm., with an abandoned cropland) to quantify the effects of varied soil surface electrochemical properties caused by soil types and plants on soil detachment on the Loess Plateau, China. A hydraulic flume test was conducted under five flow discharges (0.1, 0.2, 0.3, 0.4 and 0.6 L s-1) on a 15° slope. The results showed that large differences in soil surface electrochemical properties occurred among different soil types and plant species. The exchangeable sodium percentage (ESP), cation exchange capacity (CEC), specific surface area (S), surface charge density (σ0), surface potential (φ0) and surface electric field strength (E0) ranged from 1.02% to 2.26%, from 7.26 to 24.34 cmolc kg-1, from 8.32 to 147.38 m2 g-1, from 0.09 to 2.02C m-2, from -81.33 to -149.92 mV and from 1.23 × 108 to 28.46 × 108 V m-1, respectively. The soil detachment capacity (Dc) was significantly correlated with ESP (P < 0.01), E0 (P < 0.01) and |φ0| (the absolute value) (P < 0.05). Moreover, Dc exponentially increased with |φ0| (R2 = 0.99) and linearly increased with ESP (R2 = 0.85) and E0 (R2 = 0.95). Therefore, soil surface electrochemical properties greatly varied with soil types and plants and had a significant effect on soil detachment.


[Gastric dilatation-volvulus syndrome in guinea pigs (Cavia porcellus)].
The aim of this study was to present an overview of the gastric dilatation-volvulus syndrome in guinea pigs. Four cases of gastric dilatation-volvulus syndrome in guinea pigs were evaluated. Its clinical presentation, diagnostic options, therapeutical approach and possible alternatives thereof were discussed. Furthermore, risk factors for the disease as well as pathophysiology and etiology were discussed and compared to the situation in other species. The presented cases indicate that in addition to anamnesis and clinical examination, radiography is the means of choice to diagnose a gastric dilatation-volvulus syndrome in guinea pigs. All four patients underwent surgery. One animal was euthanized during surgery, the other three guinea pigs died postoperatively. Gastric dilatation-volvulus syndrome in guinea pigs is considered to be an emergency and, therefore, immediate stabilization is necessary, as well as surgery in almost all cases. The prognosis of this disease is guarded to poor.


Cardiac transplantation in patients over 60 years of age.
Cardiac transplant programs have routinely excluded patients over 55 years of age from consideration as transplant candidates. The Texas Heart Institute modified this policy of using age as a contraindication to transplantation. Between July, 1982, and August, 1987, a total of 200 cardiac transplants were performed, 28 (14%) of which were in patients over 60 years of age, the eldest being 66 years old at the time of transplant. Our immunosuppressive regimen consisted primarily of cyclosporine and prednisone. In 1985, azathioprine was added in an effort to decrease dosages of cyclosporine, thereby decreasing its associated nephrotoxicity. The incidences of rejection and infection were 1.2 and 1.4 episodes/patient, respectively, for those over 60 years of age versus 1.7 and 1.3 episodes/patient, respectively, for those less than 60 years of age. Of the 28 patients, 23 are alive and well. Four deaths were caused by infection, and the other by diffuse coronary arteritis. The one-year actuarial survival for patients over 60 years of age was 83%, compared with 75% for the other transplant patients. We conclude that persons over 60 years of age can undergo cardiac transplantation with results equal to or perhaps better than those of other heart transplant patients. Our experience suggests that advanced age should not be considered a major contraindication to cardiac transplantation.


Behavior and mechanism of atrazine adsorption on pristine and aged microplastics in the aquatic environment: Kinetic and thermodynamic studies.
Microplastics (MPs) are emerging pollutants that have gained much attention due to their potential harm to aquatic ecosystems and organisms. In particular, MP conjugates are loaded with chemical contaminants (e.g., atrazine pesticide), which may be ingested by organisms and can pose higher risks. However, the combined pollution effects and interaction mechanisms remain poorly understood. In this study, we systematically explored the adsorption behaviors and mechanisms of atrazine (ATZ) on pristine and aged MPs using kinetics, isotherms, and thermodynamic models. The target MPs included polystyrene (PS), polyethylene (PE), and polypropylene (PP) as well as the corresponding aged types. Moreover, the effects of pH, humic acid (HA), ionic strength, and ion species (Cl-, SO42-, HCO3-, Mg2+, and Ca2+) of aqueous factors were evaluated. The adsorption capacities of MPs under kinetic equilibrium conditions were as follows: aged PE (0.940 mg g-1) > aged PP (0.677 mg g-1) > aged PS (0.663 mg g-1) > PS (0.565 mg g-1) > PE (0.535 mg g-1) > PP (0.410 mg g-1). The adsorption kinetics and isotherm model results suggested a combination of physisorption and chemisorption. The aging process and pH significantly affected the intrinsic charge on the surface of the MPs and their adsorption capacities. Moreover, the presence of water medium parameters might enhance or inhibit adsorption of different MPs. Hydrophobic and electrostatic attraction mainly contributed to the adsorption of ATZ on pristine MPs, whereas complex surface diffusion and hydrogen bonding dominated the ATZ adsorption on aged MPs with more oxygen-containing groups. In addition, we examined the desorption performance of ATZ from MPs under simulated gastric and intestinal conditions of warm-blooded animals, and found that the ATZ desorption ratio of aged PE (35.3%) showed the most significant effects among the six target types of MPs. This study provides in-depth insights into the co-existence and complex behaviors of MPs and the pesticide pollutant ATZ, to attract further attention to their ecological risks in freshwater environments.


Correction to: Data from the COVID-19 epidemic in Florida suggest that younger cohorts have been transmitting their infections to less socially mobile older adults.
[This corrects the article DOI: 10.1007/s11150-020-09496-w.].


Liver Pathology After Hematopoietic Stem Cell Transplantation.
Hematopoietic stem cell transplantation is used to treat a variety of hematologic malignancies and autoimmune conditions. The immunosuppressive medications as well as other therapies used both before and after transplantation leave patients susceptible to a wide spectrum of complications, including liver injury. Causes for liver damage associated with stem cell transplantation include sinusoidal obstruction syndrome, graft-versus-host disease, iron overload, and opportunistic infection. Here, the authors review the clinical and pathological findings of these etiologies of liver injury and provide a framework for diagnosis.


Posterior decompression and stabilization for metastatic compression of the thoracic spinal cord: is this procedure still state of the art?
Retrospective study utilizing the standard patient data documentation of a spinal cord injury (SCI) unit. To examine the efficacy and outcome of posterior decompression and stabilization for metastatic cord compression. Orthopedic university hospital with large SCI unit. The 34 consecutive patients who had presented with symptoms of spinal cord compression due to metastatic disease and progressive neurologic deficit were treated using a uniform surgical approach (posterior decompression and stabilization). After surgery, all treatment options available in a full-featured SCI unit were applied as necessary and suitable. Outcome was rated concerning neurologic function (American Spinal Injury Association, ASIA), functional status (Functional Independence Measure) and pain. The results were compared to the published results, focusing on publications describing results of anterior surgical approaches to the spine. Evaluation of the results of the ASIA exams showed that progression of the neurologic deficit could be stopped in the majority of cases-however recovery of neurologic function was rare. The functional status could be improved markedly and good pain reduction was achieved. I mmediate surgery can be recommended if the general condition of the patient warrants surgical intervention. Using accepted standards of documentation for SCI, a clear perspective of the results that can be expected is provided. Comparing the results of this study with the current literature there is no evidence that anterior approaches are superior.


Indomethacin-induced morphological changes in the rat gastric mucosa, with or without prior treatment with two proton pump inhibitors.
The mechanisms responsible for the gastric ulcerogenic effect of indomethacin are unclear. The importance of basal acid secretion on morphological changes by indomethacin was investigated. Gastric lesions were macroscopically evaluated 6 h after indomethacin, 20 mg/kg intragastrically, in rats pre-treated with omeprazole (10-100 mumol/kg intragastrically) or lansoprazole (3-30 mumol/kg intragastrically). Glandular mucosa was processed for light, scanning and transmission electron microscopy 3 and 6 h after indomethacin in rats pre-treated with omeprazole (100 mumol/kg) or lansoprazole (30 mumol/kg). After 3 h, indomethacin caused extensive vasocongestion, oedema in the subepithelial region and superficial erosions. After 6 h, deeply extending focal necrosis involved 11% of the tissue. Leukocyte margination was occasionally seen at 3 h and consistently present at 6 h. Only at 6 h were endothelial cells altered. In rats pre-treated with omeprazole (100 mumol/kg) or lansoprazole (30 mumol/kg) grossly visible lesions were prevented. Oedema, erosions and necrosis were absent. Vasocongestion, vascular leakage and leukocytic margination were seen both at 3 and 6 h while no major damage of endothelial cells was observed. Indomethacin appears primarily to alter microcirculation, and microcirculation damage is dependent on acid for the progression to haemorrhagic lesions.


Susceptibility to stress induced visceral hypersensitivity in maternally separated rats is transferred across generations.
In irritable bowel syndrome (IBS), familial clustering and transfer across generations may largely depend on environmental factors but this is difficult to establish in the human setting. Therefore, we aimed to set up a relevant animal model. We investigated whether susceptibility to stress induced visceral hypersensitivity in maternally separated (MS) Long Evans rats can be transferred across generations without further separation protocols and, if so, whether this depends on maternal care. At adult age, we evaluated pre- vs post water avoidance (WA) changes in visceromotor response to distension in non-handled second filial generation offspring (NH-F2) of previously separated MS-F1 dams. Furthermore, the role of maternal care was evaluated by cross-fostering F2 offspring of NH-F1 and MS-F1 dams and subsequent sensitivity measurements at adult age. Involvement of mast cells in post stress hypersensitivity of NH-F2 rats was evaluated by mast cell stabilization. In adult NH-F2 offspring of MS-F1 dams, post-WA hypersensitivity to colorectal distension was observed in 80% of rats compared with 19% in offspring of NH-F1 dams. Cross-fostered pups adapted to the phenotype of the foster mother: pups of NH-F1 dams nursed by MS-F1 dams showed post-WA hypersensitivity to distension at adult age and vice versa (100% and 20% respectively). In NH-F2 rats, post-WA hypersensitivity was reversed by mast cell stabilizer doxantrazole. Maternal separated-induced susceptibility to stress-triggered visceral hypersensitivity is transferred across generations and this transfer depends on maternal care. Thus, MS is a suitable model to evaluate environmental triggers relevant to IBS clustering in families.


Psychologic factors in chronic headache: assessment by means of the SCL-90-R inventory.
A survey of the psychologic profile of 540 chronic headache cases, including migraine, tension, and mixed headache, has been carried out with the symptom check list (SCL)-90-R inventory. The results obtained were viewed in relation to sex, age, illness onset, and illness duration. Females showed a positive correlation of somatization with present age and with age at onset of illness and a negative correlation of interpersonal sensitivity, hostility, and paranoid ideation with present age and age at onset of illness. Men showed a negative correlation of obsessive-compulsive and paranoid scores with age and a positive correlation between onset of illness and somatization. Data were also analyzed by cluster analysis, which showed underpopulation with peculiar patterns of symptom profile. A prospective, long-term epidemiologic study could provide more conclusive results.


Mapping of emerging contaminants in coastal waters research: A bibliometric analysis of research output during 1986-2022.
This bibliometric analysis provides the first overview of the literature on emerging contaminants in coastal waters. Bibexcel, Microsoft Excel, VOSviewer and the bibliometix R package software were used for bibliometric analysis and science mapping. 556 publications, published between 1986 and 2022, were retrieved from the Web of Science (WoS) database. The results showed that this field of research follows Price's law of exponential growth and has exploded since 2001. Authors, journals and institutions followed Lotka's law, and Price's index (43.4 %) showed that the field is far from being obsolete. The most influential institution is the Chinese Academy of Sciences, while authors from China, USA, Japan and Singapore have the most publications and international co-authorships. The leading journal is Marine Pollution Bulletin, with a focus on Environmental Science WoS category. Hot research areas focus on risk assessment of PCBs, organochlorine compounds and personal care products in surface water and wastewater.


Systemic air embolism causing acute stroke and myocardial infarction after percutaneous transthoracic lung biopsy-a case report.
Computed tomography (CT)-guided transthoracic lung biopsy is a common procedure for the diagnosis of pulmonary lesion. Pneumothorax, pulmonary hemorrhage and hemoptysis are the most common complications of the procedure. Air embolism is a rare serious complication. We reported a case with air embolism related acute ischemic stroke and non-ST elevation myocardial infarction (NSTEMI) simultaneously after percutaneous transthoracic lung biopsy.


Degranulation plays an essential part in regulating cell surface expression of Fas ligand in T cells and natural killer cells.
Fas ligand (FasL) triggers apoptosis during cytotoxicity mediated by cytotoxic T lymphocytes and during immune downregulation. The ability of T cells and natural killer cells to trigger apoptosis through this mechanism is controlled by the cell surface expression of FasL (ref. 2). Because FasL expression is up-regulated on activation, FasL was thought to be delivered directly to the cell surface. Here we show that newly synthesized FasL is stored in specialized secretory lysosomes in both CD4+ and CD8+ T cells and natural killer cells, and that polarized degranulation controls the delivery of FasL to the cell surface. In this way, FasL-mediated apoptosis is finely controlled by receptor-mediated target-cell recognition. The cytoplasmic tail of FasL contains signals that sort FasL to secretory lysosomes in hemopoietic cells. This pathway may provide a general mechanism for controlling the cell surface appearance of proteins involved in immune regulation.


Fragility and spiralization anomalies of the chromosomes in three cases, including fraternal twins, with Fanconi's anemia, type Estren-Dameshek.
Fraternal twins, offspring of consanguineous parents, developed pancytopenia, the boy at 7, the girl at 12 years of age. A third patient became anemic at 3 years. All three are free of associated malformations. In blood cultures the incidence of chromatid breaks, exchanges, and chromosome-type aberrations was elevated to 24%, 18%, and 28%, respectively. In addition, in a low number of mitotic cells unusual observations, pointing to profound disturbances of chromosome structure, were made. It is suggested that these patients have a genetic defect impairing the normal process of mitotic chromosome condensation and decondensation.


High-performance liquid chromatographic investigation of the amino acid, amino sugar and neutral sugar content in glycoproteins.
A methods for the simultaneous separation and determination of amino acids, amino sugars and neutral carbohydrates is described. Stepwise elution systems with sodium citrate and borate buffers have developed for the ion-exchange liquid chromatographic separation of amino acids and sugars, using 8-micrometer particle size resins and the Stein and Moore and orcinol colorimetric method for detection. With the aid of this system, the direct quantitative comparison of sugars and amino acids by liquid chromatography becomes possible for the first time.


[Primary drug resistance in Mycobacterium tuberculosis among patients with pulmonary tuberculosis and its impact on permanent disability in the Volgograd region].
In the past 5 years, there has been a rise in the number of patients with new-onset drug-resistant pulmonary tuberculosis from 32.3% to 44.0%. The pattern of primary resistance is marked by an increase in the proportion of multidrug resistant Mycobacterium tuberculosis (MBT) strains, by the steady-state level of their isolation, and by a reduction in the detection rate of unidrug resistant strains. The efficiency of treatment in pulmonary tuberculosis patients with primary MBT resistance depends on patient compliance. After 3-year follow-up, death occurred in 12.2% of the patients, the tuberculous process became chronic in 31.7%, and there was a relapse in 9.8%. The drug resistance of the causative agent affects the duration of disability due to tuberculosis to a greater extent than does multidrug resistance.


Minimum acceptable diet and associated factors among children aged 6-23 months in Ethiopia.
The health and growth of children less than two years of age can be affected by the poor quality of complementary foods and poor feeding practices even with optimal breastfeeding. In Ethiopia, empirical evidence on the minimum acceptable diet and its associated factors is limited. Therefore, this study was aimed to assess the level of minimum acceptable diet and its associated factors among children aged 6-23 months in Addis Ababa Ethiopia. An institution-based Cross-sectional study was conducted among a total of 575 mother-child pairs. A simple random sampling technique was used to recruit participants. For infant and young child feeding practices, the data collection tools were adapted from world health organizations' standardized questionnaire which is developed in 2007. Data entry and analysis were performed using EPI data version 3.1 and SPSS version 20 respectively. Bivariable and multivariable logistic regression analyses were performed to determine predictor variables. Statistical significance was declared at p-value < 0.05. In this study, the level of minimum acceptable diet was found to be 74.6%.. About 90.6 and 80.2% of the children received minimum meal frequency and dietary diversity respectively. Having a husband secondary and above educational level [AOR = 4.789(95%CI:1.917-11.967)], being a housewife [AOR = 0.351(95% CI: 0.150-0.819)], having a history of more than three postnatal follow-ups [AOR = 2.616(95%CI:1.120-6.111], Having mothers age between 25 and 34 years [AOR = 2.051(95%CI:1.267-3.320)], being male child [AOR = 1.585(95%CI:1.052-2.388)] and having children age between 18 and 23 months [AOR = 3.026(95%CI:1.786-5.128)] were some of the factors significantly associated with a minimum acceptable diet. In this study, the minimum acceptable diet among children aged 6-23 months was significantly associated with the educational status of the husband, mother's occupation, history of postnatal follow-up, age of the mother, sex of the child, and age of the child. Thus, attention should be given to educating the father, empowering mothers to have a job, promoting gender equality of feeding, and counseling on the benefit of postnatal care visits. In addition, the ministry of health should work on educating and advocating the benefit of feeding the recommended minimum acceptable diet to break the intergenerational cycle of malnutrition.


Mineralocorticoid receptor haplotype, estradiol, progesterone and emotional information processing.
Carriers of MR-haplotype 1 and 3 (GA/CG; rs5522 and rs2070951) are more sensitive to the influence of oral contraceptives (OC) and menstrual cycle phase on emotional information processing than MR-haplotype 2 (CA) carriers. We investigated whether this effect is associated with estradiol (E2) and/or progesterone (P4) levels. Healthy MR-genotyped premenopausal women were tested twice in a counterbalanced design. Naturally cycling (NC) women were tested in the early-follicular and mid-luteal phase and OC-users during OC-intake and in the pill-free week. At both sessions E2 and P4 were assessed in saliva. Tests included implicit and explicit positive and negative affect, attentional blink accuracy, emotional memory, emotion recognition, and risky decision-making (gambling). MR-haplotype 2 homozygotes had higher implicit happiness scores than MR-haplotype 2 heterozygotes (p=0.031) and MR-haplotype 1/3 carriers (p<0.001). MR-haplotype 2 homozygotes also had longer reaction times to happy faces in an emotion recognition test than MR-haplotype 1/3 (p=0.001). Practice effects were observed for most measures. The pattern of correlations between information processing and P4 or E2 differed between sessions, as well as the moderating effects of the MR genotype. In the first session the MR-genotype moderated the influence of P4 on implicit anxiety (sr=-0.30; p=0.005): higher P4 was associated with reduction in implicit anxiety, but only in MR-haplotype 2 homozygotes (sr=-0.61; p=0.012). In the second session the MR-genotype moderated the influence of E2 on the recognition of facial expressions of happiness (sr=-0.21; p=0.035): only in MR-haplotype 1/3 higher E2 was correlated with happiness recognition (sr=0.29; p=0.005). In the second session higher E2 and P4 were negatively correlated with accuracy in lag2 trials of the attentional blink task (p<0.001). Thus NC women, compared to OC-users, performed worse on lag 2 trials (p=0.041). The higher implicit happiness scores of MR-haplotype 2 homozygotes are in line with previous reports. Performance in the attentional blink task may be influenced by OC-use. The MR-genotype moderates the influence of E2 and P4 on emotional information processing. This moderating effect may depend on the novelty of the situation.


Nanodiamond enhances immune responses in mice against recombinant HA/H7N9 protein.
The continuing spread of the newly emerged H7N9 virus among poultry in China, as well as the possibility of human-to-human transmission, has attracted numerous efforts to develop an effective vaccine against H7N9. The use of nanoparticles in vaccinology is inspired by the fact that most pathogens have a dimension within the nano-size range and therefore can be processed efficiently by the immune system, which leads to a potent immune response. Herein, we report a facile approach to increase antigen size to achieve not only fast but also effective responses against the recombinant HA/H7N9 protein via a simple conjugation of the protein onto the surface of nanodiamond particles. In this study, trimeric Haemagglutinin (H7) that is transiently expressed in N. benthamiana was purified using affinity chromatography, and its trimeric state was revealed successfully by the cross-linking reaction. The trimeric H7 solution was subsequently mixed with a nanodiamond suspension in different ratios. The successful conjugation of the trimeric H7 onto the surface of nanodiamond particles was demonstrated by the changes in size and Zeta-potential of the particles before and after protein coating, Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and Western-blot analysis. Next, biofunction of the protein-nanodiamond conjugates was screened using a haemagglutination assay. A mixture containing 5 µg of trimeric H7 and 60 µg of nanodiamond corresponds to a ratio of 1:12 (w/w) of agglutinated chicken red blood cells at HA titer of 1024, which is 512-fold higher than the HA titer of free trimeric H7. After the 2nd and 3rd immunization in mice, ELISA and Western blot analyses demonstrated that the physical mixture of trimeric H7 protein and nanodiamond (1:12, w/w) elicited statistically significant stronger H7-specific-IgG response demonstrated by higher amounts of H7N9-specific IgG (over 15.4-fold with P < 0.05 after the second immunization). These results indicated a potential effect inherent to nanodiamond towards modulating immune systems, which should be further evaluated and broadly applied in nanovaccine development.


Elucidating the folding problem of helical peptides using empirical parameters.
Using an empirical analysis of experimental data we have estimated a set of energy contributions which accounts for the stability of isolated alpha-helices. With this database and an algorithm based on statistical mechanics, we describe the average helical behaviour in solution of 323 peptides and the helicity per residue of those peptides analyzed by nuclear magnetic resonance. Moreover the algorithm successfully detects the alpha-helical tendency, in solution, of a peptide corresponding to a beta-strand of ubiquitin.


The mouse dorsal raphe nucleus as understood by temporal Fgf8 lineage analysis.
Fgf8 is expressed transiently during embryogenesis at the midbrain-hindbrain border, an area that gives rise to a variety of neuronal populations including the dorsal raphe (DR) nucleus. Using an inducible Fgf8-cre allele, we identified the populations of neurons defined by Fgf8 lineage at different stages of development. When Fgf8-cre expression is induced at embryonic day 7.5 (T-E7.5), in the adult the entire DR and part of the median raphe (MnR) have Fgf8 lineage. When induced at later timepoints, Fgf8 lineage progressively ebbs from the caudal and ventral aspect of this domain, particularly on the midline. Successively excluded from Fgf8- lineage at T-E9.5 are serotonin neurons in the MnR and caudal-intrafascicular DR, followed at T-E11.5 by ventral-middle and caudal-dorsal DR. The last to show Fgf8 lineage are those serotonin neurons in the lateral wings and those at the rostral-dorsal pole of DR nucleus. Thus, the temporal succession of Fgf8 lineage correlates with organizational features of serotonin neurons in these nuclei.


Uncovering key residues responsible for the thermostability of a thermophilic 1,3(4)-β-d-glucanase from Nong flavor Daqu by rational design.
Fungal 1,3(4)-β-D-glucanases were usually applied in brewing and feedstuff industries, however, the thermostability limits the most their application. The characterized 1,3(4)-β-D-glucanase (NFEg16A) from Chinese Nong-flavor (NF) Daqu showed the highest thermostability among GH16 fungal 1,3(4)-β-D-glucanases, with half-lives of thermal inactivation (t1/2) of 44.9 min at 90 °C, so multiple rational designs were used to identify the key residues for its thermostability. Based on protein sequence and 3D structure analyses around the catalytic regions. Nine site-mutants were constructed, among which N173Y and S187A were identified as the most thermotolerant and thermolabile ones, with t1/2 values of 61 min and 14.0 min at 90 °C, respectively. Therefore, N173 and S187 were then selected as "hotspots" for site-saturation mutagenesis. Interestingly, most of the N173 and S187 variants exhibited a similar thermostability to that of N173Y and S187A, respectively, confirming their different roles in the thermostability of NFEg16A. In addition, each S187A and its surrounding substitutions (D144 N and T164 N) was independently detrimental to the thermostability of NFEg16A, since the t1/2 (90 °C) of S187A, D144 N and T164 N were 14.0 min, 20.6 min and 27.2 min, respectively. Surprisingly, combinatorial substitution of S187A with D144 N or T164 N showed positive effects on the thermostability, with the increase of t1/2 (90 °C) to 30.9 min and 63.5 min for S187A-D144 N and S187A-T164 N, respectively. More importantly, S187A-T164 N showed higher thermostability than that of wild type. In short, we successfully identified two key sites and their surrounding residues in response to the thermostability of NFEg16A and further improved its thermostability by several rational designs. These findings could be used for the protein engineering of homologous 1,3(4)-β-D-glucanases, as well as other enzyme family members with high similarities.


Sepsis and Cancer: An Interplay of Friends and Foes.
Sepsis and cancer share a number of pathophysiological features, and both result from the inability of the host's immune system to cope with the initial insult (tissue invasion by pathogens and malignant cell transformation, respectively). The common coexistence of both disorders and the profound related alterations in immune homeostasis raise the question of their mutual impact on each other's course. This translational review aims to discuss the interactions between cancer and sepsis supported by clinical data and the translation to experimental models. The dramatic improvement in cancer has come at a cost of increased risks of life-threatening infectious complications. Investigating the long-term outcomes of sepsis survivors has revealed an unexpected susceptibility to cancer long after discharge from the ICU. Nonetheless, it is noteworthy that an acute septic episode may harbor antitumoral properties under particular circumstances. Relevant double-hit animal models have provided clues to whether and how bacterial sepsis may impact malignant tumor growth. In sequential sepsis-then-cancer models, postseptic mice exhibited accelerated tumor growth. When using reverse cancer-then-sepsis models, bacterial sepsis applied to mice with cancer conversely resulted in inhibition or even regression of tumor growth. Experimental models thus highlight dual effects of sepsis on tumor growth, mostly depending on the sequence of insults, and allow deciphering the immune mechanisms and their relation with microorganisms.


Significance of nuclear EGFR and ABCG2 expression in malignant transformation of oral potentially malignant disorders.
The purpose of this study was to investigate the expression of nuclear EGFR (nEGFR) and the stem cell marker ABCG2 in oral leukoplakia (OL) and oral erythroplakia (OE) and to assess their significance as prognostic biomarkers for malignant transformation. In this study we included 50 patients with oral potentially malignant disorders (OPMD), 31 with OL and 19 with OE, in whom we examined the expression of nEGFR and ABCG2 by immunohistochemical methods. Twenty-one (42%) of 50 patients with OL and OE developed oral squamous cell carcinoma (OSCC). The malignant transformation was increased 12,84-fold (95% CI, 2.15-76.44, p = 0.005) in OPMD expressing both ABCG2 and nEGFR. Expression of nEGFR is a strong indicator of malignant transformation, unlike ABCG2 expression, respectively. Determining the co-expression of the biomarkers nEGFR and ABCG2 in OPMD may serve us to determine the risk of malignant transformation in OSCC.


The cystic vein: the significance of a forgotten anatomic landmark.
The cystic vein, a portion of biliary anatomy whose insignificance in open gallbladder surgery led to its being relegated to mythology, has been rediscovered by the magnified view of laparoscopic surgery. Its presence is an important anatomic feature that helps distinguish between cystic duct and common hepatic duct, thus diminishing the risk of inadvertent bile duct injury during laparoscopic cholecystectomy.


Common genetic driver mutation in NSCLC and their association with thromboembolic events: A retrospective study.
This retrospective study aimed to estimate the incidence, risk factors of thromboembolism events (TEs) in non-small cell lung cancer patients harboring common gene mutation, and evaluate a genetic link between oncogenes and the risk of TEs in Asian patients with NSCLC. Univariate and multivariate Cox's proportional hazards regression models were used to identify the strongest predictors of TE development and evaluate the risk of TE in patients with different gene statuses of NSCLC patients. In univariate and multivariate COX analysis, patient with squamous cell carcinoma (HR 3.01, 95% CI: [1.06,8.56]; p = 0.039), multi-site metastases (HR: 2.72; 95% CI: [1.08,6.92]; p = 0.032) or high white blood cell (WBC) (HR 3.24, 95% CI: [1.46,7.22]; p = 0.004), less hemoglobin (HGB) (HR 4.89, 95% CI: [1.90,12.64]; p = 0.001), are at higher risk of thrombosis. At the molecular level, ROS and ALK rearrangement is highly associated with TE development, with HR of 4.04 (95%CI: [1.54,10.58]; p = 0.005) and HR of 3.57 (95% CI: [1.01,12.66]; p = 0.049) in univariate analysis, and even higher in multivariate analysis. EGFR mutations seem to be a protective factor against TE in univariate analyses (HR:0.28, 95%CI [0.12,0.65], p = 0.003) but are not statistically significant in the multivariate model. No correlation between KRAS mutations and TE events in both models. Besides, a numerically higher cumulative incidence of thrombosis event was observed in patients who used TKI (HR 1.473; 95% CI: [0.682, 3.181]; p = 0.32). Our study demonstrated that driver gene mutation may increase the risk of thrombosis in non-small cell lung cancer patients. The presence of ALK/ROS rearrangements in our study is associated with an approximately threefold to fourfold increase in thrombosis risk in NSCLC patients. For advanced-stage patients who used TKI, an increased incidence of thrombosis risk and shorter follow-up were observed.


Immunoblotting demonstration of antibodies to the organic matrix of developing bovine enamel.
Antiserum was raised against an acetic acid extract of partly mineralized bovine enamel. By use of immunoblotting it was shown that rabbit antibodies react with both high and low molecular weight proteins. Most but not all of the enamel proteins isolated by different extraction solutions were antigenic identical. The blotting time was found to be important when immunoblotting of enamel proteins is carried out.


Antiviral activities of mycophenolic acid and IMD-0354 against SARS-CoV-2.
In this study, the anti-severe acute respiratory syndrome coronavirus-2 (anti-SARS-CoV-2) activity of mycophenolic acid (MPA) and IMD-0354 was analyzed. These compounds were chosen based on their antiviral activities against other coronaviruses. Because they also inhibit dengue virus (DENV) infection, other anti-DENV compounds/drugs were also assessed. On SARS-CoV-2-infected VeroE6/TMPRSS2 monolayers, both MPA and IMD-0354, but not other anti-DENV compounds/drugs, showed significant anti-SARS-CoV-2 activity. Although MPA reduced the viral RNA level by only approximately 100-fold, its half maximal effective concentration was as low as 0.87 µ m, which is easily achievable at therapeutic doses of mycophenolate mofetil. MPA targets the coronaviral papain-like protease and an in-depth study on its mechanism of action would be useful in the development of novel anti-SARS-CoV-2 drugs.


Short term ciprofloxacin and clindamycin combination antibiotic therapy before and after transrectal ultrasound scan and prostate biopsy: Its impact on major components of gut microbiome.
The perturbation of gut microbiome is a risk factor for a number of adverse conditions. Among other factors antibiotic therapy is a common culprit. We characterized the short-term alteration of gut microbiome after antibiotic therapy. Nine patients (age (median [range]): 67 [57-75 years]) were subjected to prostate biopsy. Ciprofloxacin and clindamycin, 500 mg and 150 mg, respectively, were administered twice a day; this combination therapy was started the day before and continued until 5th and 8th day, respectively, following biopsy. 16s RNA sequencing data from fecal swabs taken before antibiotic therapy and 14 days after biopsy were analysed. At phylum level, the abundance of Actinobacteria and Firmicutes decreased, while that of Bacteroides and Proteobacteria increased after antibiotic therapy. The ratio of Firmicutes:Bacteroides inversed (from 2.81 to 0.74, p = 0.035). At order level, the abundance of Bacteroidales and Veillonellales increased, while that of Clostridiales and Coriobacteriales decreased. At genus level the abundance of Bacteroides increased, while those of Roseburia, Faecalibacterium and Collinsella decreased. These findings indicate that short-term antibiotic exposure skews gut microbiome composition. The current level of knowledge does not allow to decide whether this skewness is detrimental and has any long-term effect on disease including prostate pathology.


Behavioral relaxation training for tremor disorders in older adults.
Two adult men, aged 86 and 63, with essential tremor and Parkinson's-disease-related tremor, respectively, were provided Behavioral Relaxation Training in reclined and upright seated positions. Multiple measures were recorded, including the Behavioral Relaxation Scale (BRS), clinical and self-rated tremor severity, informant ratings, ratings of disability in activities of daily living (ADL), and forearm EMG. Results showed increased relaxation skills on the BRS, with reductions in EMG, tremor ratings, and some ADL disabilities. Upright BRS scores did not change during reclined training, but improved rapidly during upright training. The second man was found to suffer from dyskinesia when he relaxed during baseline, which declined markedly during training. A two-week follow-up indicated that most improvements were maintained by both men. Statistical analyses of data for each man showed significant changes. These results suggest that relaxation may be useful in the treatment of idiopathic and pathologic tremor disorders in older adults.


Variations in perceived stress among Syrian refugee parents resettled through different sponsorship programs in Canada.
Little is known about the perceived stress level of Syrian Refugee (SR) parents residing in Canada specifically in relation to different sponsorship programs. This study aims to assess the relationship between the different sponsorship programs [Government-Assisted Refugees (GAR), Privately Sponsored Refugees (PSR) and Blended Visa Office-Referred refugees (BVOR)] and perceived stress among SR parents, with at least one child under the age of four, who resettled in the Greater Toronto area after 2015. A convenience sample of 155 Syrian Refugee (SR) parents was recruited. Perceived levels of stress were measured using the Perceived Stress Scale (PSS-10). Multiple linear regression analysis was performed to assess the independent relation between several types of sponsorship programs and PSS adjusting for demographic, economic and social factors. The overall average PSS score was found to be 12.5 ± 7.2 with BVORs presenting the highest level of moderate stress when compared to GARs and PSRs (75.0% compared to 39.5% and 35.2% respectively). Multivariate analysis showed that the mean PSS was significantly higher among BVORs when compared with GARs (Adj β = 4.8; 95% CI 0.4, 9.2). No significant difference in PSS levels was reported when PSRs were compered to GARs. Increased PSS scores were found to be associated with worse family functioning (Adj β = 4.2; 95% CI 1.0, 7.4), while decreased PSS scores were associated with increased age (Adj β = -0.4; 95% CI -0.6, -0.1). A better understanding of the various underlying factors associated with elevated stress is essential for improving the quality of life for SRs in Canada. Results of the study may help tailor more effective preventative measures or government interventions dedicated to reducing stress levels among this population.


The Royal College of Nursing guidance on responding to a request to hasten death.
In July 2009, when the Royal College of Nursing (RCN) Council in the UK moved to a neutral position on assisted suicide, it also determined that guidance for its members was needed. In October 2011 this guidance was finally published (RCN, 2011). Here the context, scope, and content of this publication are considered.


Angiotensinogen mRNA. Regulation by cell cycle and growth factors.
The components of the renin-angiotensin system have been colocalized in many tissues suggesting that local generation of angiotensin II can regulate blood flow in specific organs or tissues. This in combination with the fact that proliferating tissues require angiogenesis and increased blood flow to develop have led us to study the relationship of angiotensinogen mRNA production to cell cycle regulation. Reuber H35 (H4IIE) cells were growth-arrested by serum deprivation. Cells were then treated with 10% fetal calf serum, depleted serum, or insulin. Insulin and serum were equally potent at increasing beta-actin mRNA levels, depressing angiotensinogen mRNA levels, and in increasing [3H]methyl thymidine incorporation. The half-maximal insulin effect occurred at 5 x 10(-9) M. Insulin-like growth factor I and II had no effect on any of the parameters measured. 12-O-tetradecanoyl phorbol 13-acetate (TPA) also induced beta-actin mRNA, decreased angiotensinogen mRNA, and caused an increase in [3H]methyl thymidine incorporation. The TPA effects were of shorter duration and of lower magnitude than those caused by insulin or serum. Inactivation of protein kinase C by preincubation with TPA did not block the insulin response. TPA has been shown to induce angiogenesis in vitro. Thus, these studies suggest that inhibition of angiotensinogen gene activity may be part of the proliferative or angiogenic process. Our experimental data may provide a model for further experimental dissection of the biochemical steps involved in angiogenesis.


LINC00958 facilitates cervical cancer cell proliferation and metastasis by sponging miR-625-5p to upregulate LRRC8E expression.
Accepted as a malignant tumor worldwide, cervical cancer (CC) has attracted much attention for its high incidence and mortality rates. Previous studies have elucidated the critical regulatory function that long noncoding RNAs (lncRNAs) exert on the tumorigenesis and progression of diverse tumors. Although multiple investigations have depicted that LINC00958 has a great impact on the complex biological process of many cancers, knowledge concerning the regulatory role of LINC00958 in CC remains limited and needs to be further explored. In our study, LINC00958 expression was evidently overexpressed in CC tissues and cells. Besides this, LINC00958 negatively regulated miR-625-5p expression and was verified to bind with miR-625-5p in CC. Subsequently, it was testified by a series of experiments that LINC00958 promotes CC cell proliferation and metastasis by sponging miR-625-5p. Furthermore, the leucine-rich repeat containing the eight family member E (LRRC8E) could bind with miR-625-5p, and its expression was negatively modulated by miR-625-5p, whereas positively regulated by LINC00958 in CC. Final rescue assays verified the effects of LINC0095/LRRC8E interaction and miR-625-5p/LRRC8E interaction on CC cell proliferation and metastasis. Collectively, LINC00958 facilitates CC cell proliferation and metastasis via the miR-625-5p/LRRC8E axis.