The outcomes of right-sided and left-sided colonic diverticulitis following non-operative management: a systematic review and meta-analysis.
There is no sufficient overview of outcomes in right-sided and left-sided colonic diverticulitis (CD) following non-operative management. This systematic review was conducted to evaluate the recurrence/treatment failure in right-sided and left-sided CD. A systematic review was conducted following PRISMA guidelines. MEDLINE, Embase, and Cochrane Library from inception to Dec 2021 were searched. The study characteristics, recurrence/treatment failure, and risk factors for recurrence/treatment failure were extracted. Proportional meta-analyses were performed to calculate the pooled recurrent/treatment failure rate of right-sided and left-sided CD using the random effect model. Logistic regression was applied for the factors associated with the recurrence/treatment failure. Thirty-eight studies with 10,129 patients were included, and only two studies comprised both sides of CD. None of the studies had a high risk of bias although significant heterogeneity existed. The pooled recurrence rate was 10% (95% CI 8-13%, I2 = 86%, p < 0.01) in right-sided and 20% (95% CI 16-24%, I2 = 92%, p < 0.01) in left-sided CD. For the uncomplicated CD, the pooled recurrence rate was 9% (95% CI 6-13%, I2 = 77%, p < 0.01) in right-sided and 15% (95% CI 8-27%, I2 = 97%, p < 0.01) in the left-sided. Age and gender were not associated with the recurrence of both sides. The treatment failure rate was 5% (95% CI 2-10%, I2 = 84%, p < 0.01) in right-sided and 4% (95% CI 2-7%, I2 = 80%, p < 0.01) in left-sided CD. The risk factors for recurrence and treatment failure were limited. Non-operative management is effective with low rates of recurrence and treatment failure for both right-sided and left-sided CD although left-sided exhibits a higher recurrence. The recurrence rates did not differ between patients receiving antibiotics or not in uncomplicated CD. Age and sex were not associated with the recurrence although other risk factors were dispersing. Further risk factors for recurrence and treatment failure would be investigated for precise clinical decision-making and individualized strategy.


Neural network and cubist algorithms to predict fecal coliform content in treated wastewater by multi-soil-layering system for potential reuse.
This study aims to find the most accurate machine learning algorithms as compared to linear regression for prediction of fecal coliform (FC) concentration in the effluent of a multi-soil-layering (MSL) system and to identify the input variables affecting FC removal from domestic wastewater. The effluent quality of two different designs of the MSL system was evaluated and compared for several parameters for potential reuse in agriculture. The first system consisted of a single-stage MSL (MSL-SS), and the second system consisted of a two-stage MSL (MSL-TS). The concentration of FC in the effluent of the MSL-TS system was estimated by three machine learning algorithms: artificial neural network (ANN), Cubist, and multiple linear regression (MLR). The accuracy of the models was measured by comparing the real and predicted values. Significant (p < .001) improvements were noted for the removal of pollutants by the MSL-TS system compared with the MSL-SS system. Overall, the water quality parameters investigated complied with FAO irrigation standards. The predictive performance of the models has been compared and evaluated using several metrics. The results revealed that the ANN model yielded a superior predictive performance (R2 = .953), followed by the Cubist model (R2 = .946) and the MLR technique (R2 = .481). Based on the accurate model (ANN), the degree of influence of each predictor was investigated, and the results show that total suspended solids and pH have proved to be more useful for predicting FC concentrations.


Interactive effect of exogenous protease enzyme and dietary crude protein levels on growth and digestibility indices in broiler chickens during the starter phase.
This study was conducted to study the effect of protease as well as three dietary crude protein levels on growth and nutrient digestibility in broilers. The broiler chickens (n = 540) were assigned to six dietary treatments with six replicates. Three dietary crude protein (CP) levels (17, 19, and 21%) along with two levels of protease (0 and 30,000 IU/kg) were investigated in 3 × 2 factorial arrangement during the starter phase. Body weight was higher (P < 0.05) in group fed with CP-21; however, feed intake was significantly (P < 0.05) lower in CP-19 and CP-21. Resultantly, FCR was significantly (P < 0.05) improved in birds fed with CP-21. Similarly, body weight, feed intake, and FCR were significantly (P < 0.05) improved in enzyme-treated birds compared to the untreated birds. For practical purpose, birds fed CP-19 with protease enzyme resulted in improved FCR compared to birds fed with CP-21. The results revealed that CP and apparent metabolizable energy (AME) were significantly (P < 0.05) higher in birds fed with CP-21 along with supplementation of enzyme while abdominal fat was significantly (P < 0.05) lower in the same group compared to birds fed with CP-17. These results indicated that a diet having 21% CP supplemented with 30,000 IU/kg protease enzyme was superior in improving the performance and digestibility of nutrients in broiler during the starter phase.


Extraction and incorporation of bioactives into protein formulations for food and biomedical applications.
Bioactive compounds from natural resources have been pointed out as promising substances with great benefits for human health. Furthermore, new techniques for their extraction have been reviewed in order to consider a global approach taking economic and environmental issues into account. Additionally, the incorporation of these biologically active compounds into protein-based products manufactured via different processing methods, such as solution casting, compression moulding, electrospinning, freeze-drying, and 3D printing, has been assessed, since the design and manufacturing method employed have a direct influence into the final properties of the material. Hence, new opportunities to develop active biopolymeric materials with great potential in food and biomedical applications have been presented. This review aims to provide an overview of some advanced technologies employed for bioactive extraction, as well as the bioactives incorporation into protein formulations to produce biomaterials and food packaging.


Future directions in managing aniridia-associated keratopathy.
Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.


An examination of whether human placental perfusion allows accurate prediction of placental drug transport: studies with diazepam.
Presently, no well-validated predictive tools are available for human placental transfer. We studied the transplacental passage of diazepam (DZP) in a recirculating dual human placental perfusion and compared the data with in vivo clinical data from the literature. Term placentas from healthy mothers without medication were used. The dual, recirculating perfusion technique was used. DZP (2 microg/ml, n = 4; 200 ng/ml, n = 3) and the reference compound antipyrine (100 microg/ml) were added into the maternal circulation simultaneously. The disappearance of drugs from the maternal circulation and appearance into the fetal circulation were followed every 15 min for 2 h. DZP was detectable in the fetal circulation within 15 min in all of the perfusions indicating rapid transfer. DZP concentrations in the maternal circulation were higher than in the fetal circulation throughout the perfusion with both initial concentrations. At the end of the perfusion, the feto-maternal ratio was 0.48 +/- 0.11 (mean +/- S.D.) and the transfer from the maternal to the fetal compartment 18.4 +/- 3.6% with 2 microg/ml of DZP and 0.55 +/- 0.10 and 20.5 +/- 3.1% with 200 ng/ml of DZP, respectively. DZP concentrations in the perfused area of the placenta were in average 2 times higher than in the maternal perfusate and 3.6 times higher than in the fetal perfusate. Total recovery of DZP from samples, perfusion fluid, and perfused tissue was 37.6 +/- 21%. Since animal studies in vivo do not accurately predict human placental transfer and it is problematic to study placental transfer of drugs in humans in vivo, the present human placental perfusion system could serve as one part of a test battery for fetotoxicity. However, although our earlier studies and those from the literature indicate a good correlation between in vivo and placental perfusion data, the present study shows this is not the case for all drugs.


Protamine as a potential amoebicidal agent for contact lens disinfection.
To evaluate the amoebicidal efficacy of protamine with polyhexamethylene biguanide (PHMB) and ethylenediamine tetraacetic acid (EDTA). The International Organization for Standardization 14729:2001 procedure was modified to test amoebicidal activity. Acanthamoeba cells were inoculated into dilutions of protamine alone (57 to 228 μM) or in combination with PHMB/EDTA and incubated at 25°C for 6 hours. The number of survivors was determined after 7 days of incubation at 32°C on Escherichia coli-seeded agar plates. For encystment, Acanthamoeba trophozoites were incubated in protamine/PHMB/EDTA for 24 hours, and then the number of cysts was counted using a hemocytometer. Protamine showed significant (p < 0.01) activity against trophozoites of both Acanthamoeba strains, which reached 2 log reductions or more for 228 μM compared with that in phosphate buffered saline. The addition of PHMB to protamine significantly (p = 0.002) improved anti-Acanthamoeba effect (0.8 logs reduction) of Acanthamoeba castellanii only. The addition of EDTA to protamine/PHMB only slightly improved efficacy (0.1 logs). Protamine at 228 μM significantly (p < 0.0001) killed the cysts of either strain by between 0.6 and 0.9 logs. Protamine/PHMB significantly increased killing (p = 0.014) of cysts of A. castellanii only. Protamine/PHMB/EDTA did not show synergy against Acanthamoeba cysts. Protamine or protamine/PHMB with or without EDTA did not cause encystment. Protamine shows good activity against Acanthamoeba trophozoites and cysts and works more effectively in combination with PHMB against A. castellanii. Protamine may be a promising ingredient in contact lens-disinfecting solutions to control Acanthamoeba growth.


Muscarinic receptor subtypes in human and guinea pig lung.
Muscarinic receptor subtypes in human and guinea pig lung membranes were characterised using selective muscarinic antagonists. Competition experiments were carried out against [3H](-)-quinuclidinyl benzilate binding at 25 degrees C in Tris-HCl buffer; non-specific binding was determined in the presence of 1 microM atropine. Of all the antagonists examined, only the M1-selective antagonist pirenzepine exhibited a heterogeneous binding profile (nH less than 1.0), best described by two-binding sites of high and low affinity. Binding of [3H]pirenzepine confirmed the presence of a high proportion of high affinity (M1) receptors (60% of total) in human peripheral lung. The high potency of M3-selective antagonists 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) and hexahydrosiladifenidol suggested the presence of M3 receptors, but the low potency of AF-DX 116 and methoctramine indicated that there was no significant population of M2 receptors present. The existence of muscarinic receptor subtypes in lung may have important clinical implication but their cellular localisation remains to be determined.


Acupressure versus dilution of fentanyl to reduce incidence of fentanyl-induced cough in female cancer patients: a prospective randomized controlled study.
Fentanyl-induced cough (FIC) is a transient condition with a reported incidence of 18% to 65% depending on the dose and route of administration of fentanyl. Nonpharmacological methods to prevent FIC are more cost-effective than medications. Dilution of fentanyl has a proven role in the prevention of FIC. Acupressure can also prevent FIC because it has a proven role in the treatment of cough. This study included 225 female patients with an American Society of Anesthesiologists physical status of I or II who were randomly divided into 3 groups of 75 patients each. Patients in the control group received undiluted fentanyl at 3 µg/kg, patients in the acupressure group received undiluted fentanyl at 3 µg/kg with acupressure, and patients in the dilution group received diluted fentanyl at 3 µg/kg. Coughing was noted within 2 min of fentanyl administration. The severity of FIC was graded as mild (1-2 coughs), moderate (3-4 coughs), or severe (≥5 coughs). The timing of coughs was also noted. The incidence of FIC was 12.7% in the control group, 6.8% in the dilution group, and 1.3% in the acupressure group. The difference in the incidence of cough was statistically significant (P = 0.008) between the control and acupressure groups. The difference in the severity of cough among the groups was not statistically significant. The median onset time of cough among all groups was 9 to 12 seconds. The application of acupressure prior to administration of fentanyl significantly reduces the incidence of FIC. Dilution of fentanyl also reduces the incidence of FIC, but the difference is not statistically significant.


Movement control strategies during jumping in a lizard (Anolis valencienni).
Whereas maximal performance is subjected to specific control criteria, sub-maximal movements theoretically allow for an infinite number of control strategies. Yet sub-maximal movements are predominant in the locomotor repertoire of most organisms and often little understood. Previous data on sub-maximal vertical jumping in humans has suggested that a movement effectiveness criterion might best explain the observed control strategy employed. Here we test the generality of this criterion in jumping by inducing lizards to jump both at a range of distances as well as a range of take-off angles. Our results show that while movement effectiveness appears to best explain jumping for different take-off angles, a 'push harder' strategy (i.e. mostly increasing the force output of the system), is used in the control of distance jumping. Thus, our data support the generality of the movement effectiveness criterion for vertical jumping, but not for distance jumping. Sub-maximal distance jumping in the lizard Anolis valencienni appears to be governed by a relatively simple control strategy that allows a rapid response. This accords well to the ecological circumstances in which long jumps are typically used (escape from predators).


Internalised stigma in people with rheumatoid arthritis: a cross sectional study to establish the psychometric properties of the ISMI-RA.
Internalised stigma is theorized to be the internalisation and legitimisation of stereotypes of the diagnosis held in society and has not been quantified within patients with Rheumatoid Arthritis. This study aimed to: validate a modified version of a measure of internalised stigma, (the Internalised Stigma of Mental Illness scale, ISMI) for use in a group of patients diagnosed with rheumatoid arthritis; establish the consistency of the construct being measured, and to explore the levels of internalised stigma within this group. A cross-sectional survey was conducted in London, UK with participants receiving out-patient treatment for Rheumatoid Arthritis. Participants completed the ISMI-Rheumatoid Arthritis (ISMI-RA) and a measure of self-esteem. One hundred respondents were interviewed by phone. The ISMI-RA was found to be reliable using a measure of internal consistency (α = 0.85) showed concurrent validity with the Index of Self Esteem (r = 0.58, p < 0.01) and discriminant validity with no association with gender (t = 1.43, p = 0.61). A quarter of respondents reported internalised stigma to a 'severe' level. Acceptability and feasibility were established. A confirmatory factor analysis provided some support for the model of internalised stigma. The application of the ISMI-RA among the Rheumatoid Arthritis population looks promising. Internalised stigma was found to be present within this group. More research is needed to generalize these results and to explore the effects of internalised stigma on treatment adherence and quality of life.


Medicolegal causation: a source of professional misunderstanding.
The authors of this Comment--a lawyer and a physician--suggest that most physicians who are called upon to testify concerning medical issues in personal injury litigation do not understand that judges and attorneys view "causation" quite differently than do members of the medical community. For example, medical practitioners tend to be concerned with all possible causes of the patient's current medical condition, whereas legal practitioners in personal injury cases generally focus on a particular event as possibly precipitating, hastening, or aggravating a particular aspect of the patient's condition to the extent that the event in question is, in legal language, the "proximate cause" of an injurious result. The authors summarize and analyze the differences--and the occasional similarities--between the medical and the legal approaches to causation, in the hope that they will thereby (1) contribute to greater understanding by the two professions of each other's theory and practice, and (2) help the expert medical witness to be more comfortable and more effective in his courtroom role.


Methods of assessment of the arterial pulse wave in normal human pregnancy.
The study was undertaken to obtain normal values for characteristics of the peripheral arterial pulse wave, in nonpregnant women and in pregnant women at three different stages of gestation, with two devices, to describe cardiovascular hemodynamic variables induced by pregnancy. Sixty pregnant women were enrolled in the study at three stages of pregnancy, 17 to 20 weeks, 25 to 28 weeks, and 33 to 36 weeks gestation. Results are presented for 53 of these subjects who remained normotensive throughout pregnancy. The values measured were compared with those from 10 nonpregnant women. The two devices used were the SphygmoCor and a monitor invented and developed by Professor Edward Hon, not yet commercially available, referred to in this article as the "Hon" monitor. An increase in heart rate was observed in all pregnant women. Blood pressure values were lower in pregnancy than in normal nonpregnant women. With respect to the SphygmoCor, the time from the start of the arterial waveform to the second peak/shoulder, was significantly shorter, and augmentation pressure and augmentation index were significantly lower in pregnancy. Data obtained from the "Hon" monitor showed no significant differences in pulse wave arrival time, but rapid ejection time was significantly shortened in pregnancy. The clinical findings confirm the known cardiovascular changes of pregnancy associated with vasodilatation of peripheral vessels and expansion of blood volume. The fall in augmentation pressure and index are consistent with these changes. Rapid ejection time and the time from the start of the arterial waveform to the second peak/shoulder, which should reflect similar cardiovascular physiologic events, were weakly correlated.


On line vapor generation of osmium based on solution cathode glow discharge for the determination by ICP-OES.
A novel plasma induced vapor generation method is proposed to determine osmium in solutions. Without any chemical oxidizing agents, osmium ion can be readily converted to volatile osmium tetraoxide vapor in the solution cathode glow discharge (SCGD) system. The generated osmium vapor is then transported to inductively coupled plasma for determination by optical emission spectrometry. The influences of background electrolyte, carrier gas flow rate, sample flow rate, ICP power and discharge current were investigated. The analytical performances of this proposed technique were evaluated under optimized conditions. The detection limit of Os was calculated to be 0.51 ng mL(-1). The reproducibility, expressed as the relative standard deviation (n=11) of a 2.0 μg mL(-1) standard solution, was 1.9%. This SCGD induced vapor generation is sensitive and simple, oxidation reagents free, providing an alternative analytical method for measuring Os in geological or environmental water samples.


Posterior intravaginal slingplasty for vaginal prolapse.
To evaluate the results of the posterior intravaginal slingplasty (IVS). From a urogynecology database, 42 patients who had undergone posterior IVS procedures were analyzed. All the selected patients had also had a posterior colporrhaphy (88% with mesh inserted into the rectovaginal space). Intraoperatively, there was one complication, a rectum perforation. All patients were followed-up, with a median of 13 months. Recurrent prolapse, grade 3 or 4, developed in 12 patients (29%) which included ten cystoenteroceles (24%), four rectoenteroceles (10%), and three cases of utero/vault prolapse (7%). Repeat surgery was performed in six patients (14%). For utero/vault prolapse, eight patients presented preoperatively with grades 3 and 4 prolapse. On follow-up, three patients had utero/vault prolapse, one of whom did not have utero/vault prolapse on presentation. Therefore, of the eight patients presenting with utero/vault prolapse, only two had repeat prolapse on follow-up, which reflected an improvement of 75%. The posterior IVS delivered satisfactory results for vault and posterior compartment prolapse, with a 75% improvement in vault prolapse. It was not possible, however, to separate the effect of posterior IVS and posterior colporrhaphy on the prevention of recurrent prolapse nor on the improvement of difficulty in defecation. Due to the utilization of the now-abandoned vaginal anterior colposuspension procedure for the treatment of anterior compartment prolapse, no conclusions regarding the impact of the posterior IVS on the anterior compartment can be made.


1DTempPro V2: New Features for Inferring Groundwater/Surface-Water Exchange.
A new version of the computer program 1DTempPro extends the original code to include new capabilities for (1) automated parameter estimation, (2) layer heterogeneity, and (3) time-varying specific discharge. The code serves as an interface to the U.S. Geological Survey model VS2DH and supports analysis of vertical one-dimensional temperature profiles under saturated flow conditions to assess groundwater/surface-water exchange and estimate hydraulic conductivity for cases where hydraulic head is known.


Erosive reflux disease increases risk for esophageal adenocarcinoma, compared with nonerosive reflux.
Gastroesophageal reflux disease is a strong risk factor for esophageal adenocarcinoma, but it is not clear whether the mucosal inflammation that develops in patients with reflux disease promotes this cancer. We determined the development of adenocarcinoma among patients who underwent esophagogastroduodenoscopy and were found to have erosive (with esophagitis) or nonerosive (without esophagitis) reflux. We performed a nationwide cohort study using data from 33,849 patients with reflux disease (52% men; median age, 59.3 y) from population-based Danish medical registries, from 1996 through 2008. The observed incidences of adenocarcinoma were compared with the expected incidence for the general population, standardized by age, sex, and calendar time. Absolute risks were estimated using Kaplan-Meier methods. In the study cohort, 26,194 of the patients (77%) had erosive reflux disease and 37 subsequently developed esophageal adenocarcinoma after a mean follow-up time of 7.4 years. Their absolute risk after 10 years was 0.24% (95% confidence interval [CI], 0.15%-0.32%). The incidence of cancer among patients with erosive reflux disease was significantly greater than that expected for the general population (standardized incidence ratio, 2.2; 95% CI, 1.6-3.0). In contrast, of the 7655 patients with nonerosive reflux disease, only 1 was diagnosed with esophageal adenocarcinoma after 4.5 years of follow-up evaluation (standardized incidence ratio, 0.3; 95% CI, 0.01-1.5). Erosive reflux disease, but not nonerosive disease, increased the risk of esophageal adenocarcinoma, based on analysis of population-based Danish medical registries. Inflammation therefore might be an important factor in the progression from reflux to esophageal adenocarcinoma.


Translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20) facilitates cancer aggressiveness and therapeutic resistance in chondrosarcoma.
Chondrosarcoma is the second most common primary bone malignancy, representing one fourth of all primary bone sarcomas. It is typically resistant to radiation and chemotherapy treatments. However, the molecular mechanisms that contribute to cancer aggressiveness in chondrosarcomas remain poorly characterized. Here, we studied the role of mitochondrial transporters in chondrosarcoma aggressiveness including chemotherapy resistance. Histological grade along with stage are the most important prognostic biomarkers in chondrosarcoma. We found that high-grade human chondrosarcoma tumors have higher expression of the mitochondrial protein, translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20), compared to low-grade tumors. TOMM20 overexpression in human chondrosarcoma cells induces chondrosarcoma tumor growth in vivo. TOMM20 drives proliferation, resistance to apoptosis and chemotherapy resistance. Also, TOMM20 induces markers of epithelial to mesenchymal transition (EMT) and metabolic reprogramming in these mesenchymal tumors. In conclusion, TOMM20 drives chondrosarcoma aggressiveness and resistance to chemotherapy.


Structural determinants of cytochrome P450 substrate specificity, binding affinity and catalytic rate.
The structural characteristics of cytochrome P450 substrates are summarised, showing that molecular descriptors can discriminate between chemicals of differing P450 isozyme specificity. Procedures for the estimation of P450 substrate binding interaction energies and rates of metabolism are described, providing specific examples in both individual compounds binding to P450s, including those of known crystal structure, and within series of structurally related chemicals. It is demonstrated that binding energy components are primarily hydrophobic/desolvation and electrostatic/hydrogen-bonded in nature, whereas electronic factors are of importance in determining variations in reaction rates. It is thus shown that the prediction of P450 substrate binding affinities and catalytic rates may be feasible, provided that sufficient structural information is available for the relevant enzyme-substrate complex.


[A case of partial 1p36.1 deletion and partial trisomy 6p diagnosed by karyotype].
The deletion of chromosomal region 1p36 is one of the most common sub-telomeric microdeletion syndromes and has distinctive dysmorphic features. On the other hand, partial trisomy of the short arm of chromosome 6 is a rare chromosomal abnormality with a variable phenotype. To report a case with both chromosome abnormalities, and to highlight the importance of the karyotype as a diagnostic tool in dysmorphology. The case of is presented of a two month-old infant with several craniofacial anomalies, neck haemangioma, sacral pit, rhizomelic shortening, small hands and feet, left unilateral cryptorchidism, and hypotonia. The infant also suffered intrauterine growth restriction and is the product of the eighth pregnancy of a 28 years old woman. Due to the unspecific findings in phenotype, a karyotype was requested, which showed a partial deletion of 1p36.1 and a partial trisomy of chromosome 6. The development of new techniques in molecular biology has improved diagnostic possibilities in medical genetics. However, the traditional karyotype remains as an important diagnostic tool in patients with multiple congenital anomalies.


Music beyond sounds and its magic in the clinical process.
This paper highlights the role of music in psychic change through a clinical case. A patient, who was initially distant and cold, started to talk about music. An enactment around the analyst's comment about a famous conductor, started an exchange of music "notes" that changed the course of treatment. For the analyst, it brought old memories and musical reveries. For the patient, music allowed him to be in touch with undiscovered parts of himself and losses that had not been mourned. There was a mutual personal transformation and expanding awareness of self and other for both participants.


Serially coupling hydrophobic interaction and reversed-phase chromatography with simultaneous gradients provides greater coverage of the metabolome.
The serial coupling of a reversed-phase liquid chromatography (RPLC) column to a hydrophilic interaction liquid chromatography (HILIC) column has been developed in recent years for the detection of polar and nonpolar metabolites. TCA intermediates, bile acid standards and numerous polar and non-polar metabolites extracted from beer were analysed using a combined RPLC/HILIC method. Non-polar metabolites were retained by the RPLC column. Polar metabolites not retained by the RPLC column were retained and separated by the HILIC column. The results from this study validate this simple yet powerful metabolomics approach.


Fast adsorption of heavy metal ions by waste cotton fabrics based double network hydrogel and influencing factors insight.
Massive consumption of cotton fabrics has brought up a serious problem concerning the waste cotton fabrics (WCFs) disposal. It is widely accepted that if WCFs can be reutilized, there will be great business potentials. Herein, we prepared a double network hydrogel based on WCFs and polyacrylamide (Cellulose/PAM DNHs) for heavy metal removal. The DNHs exhibit fast kinetics that sorption equilibrium is achieved in 5min because of the porous and sheet-like laminar structures they possess. The DNHs also illustrate excellent adsorption property and good reusability. The tandem two columns packed with Cellulose/PAM-3 can effectively process simulated and practical wastewater, and the adsorption discrepancy is negligible after three adsorption-desorption cycles. The treatment volumes of simulated wastewater are 172.5 BV (7935mL), 195 BV (8970mL), and 292.5 BV (13455mL) for Cd(II), Cu(II), and Pb(II), respectively. Furthermore, the treatment volumes of practical industrial wastewater reach 42 BV (1932mL) for Cd(II), 63 BV (2898mL) for Cu(II), and 87 BV (4002mL) for Zn(II), Pb(II) and Fe, respectively. This work provides a new avenue for the combination of WCFs reuse and heavy metal removal, which is of great importance to the construction of resource sustainability and environment-friendly society.


Selective labeling by propidium iodide injected into the lateral cerebral ventricle of the rat.
Injections of propidium iodide (PI) into the lateral cerebral ventricle of the rat resulted in a bilateral labeling in the septohippocampal nuclei, substantia nigra (SN), ventral tegmental area (VTA), retrorubral nuclei (rr), dorsal and median raphe nuclei, regions within and dorsal to the medial lemniscus of the caudal midbrain, and Purkinje cells in the cerebellum. No labeled neurons were seen in other areas of the brain. The data suggest that PI appears to exhibit selective labeling, and the mechanism underlying the selective labeling is discussed. Combined with Faglu histofluorescence, it was found that all PI-labeled cells in SN-VTA-rr were catecholamine (CA) neurons. After a transection of the medial forebrain bundle immediately before the PI injection, an accumulation of PI was only seen in the distal segments of severed nigrostriatal CA fibers. This provides a strong evidence that PI labeling of CA cells in SN-VTA-rr is due to axonal uptake and retrograde transport.


New Predictive Resting Metabolic Rate Equations for High-Level Athletes: A Cross-Validation Study.
The present study aims a) to assess the agreement between the measured resting metabolic rate (RMR) using indirect calorimetry and different predictive equations (predicted RMR), and b) to propose and cross-validate two new predictive equations for estimating the RMR in high-level athletes. The RMR of 102 athletes (44 women) was assessed using indirect calorimetry, whereas the body composition was assessed using skinfolds. Comparisons between measured and predicted RMR values were performed using one-way ANOVA. Mean difference, root mean square error (RMSE), simple linear regression, and Bland-Altman plots were used to evaluate the agreement between measured and predicted RMR. The accuracy of predictive equations was analyzed using narrower and wider accuracy limits (±5% and ±10%, respectively) of measured RMR. Multiple linear regression models were employed to develop the new predictive equations based on traditional predictors (equation 1) and the stepwise method (equation 2). The new equations 1 and 2 presented good agreement based on the mean difference (3 and -15 kcal·d -1 ), RMSE (200 and 192 kcal·d -1 ), and R2 (0.71 and 0.74), respectively, and accuracy (61% of subjects between the limit of ±10% of measured RMR). Cunningham's equation provided the best performance for males and females among the existing equations, whereas Jagim's equation showed the worst performance for males (mean difference = -335 kcal·d -1 ; RMSE = 386 kcal·d -1 ). Compared with measured RMR, most predictive equations showed heteroscedastic distribution (linear regression's intercept and slope significantly different from zero; P ≤ 0.05), mainly in males. The new proposed equations can estimate the RMR in high-level athletes accurately. Cunningham's equation is a good option from existing equations, and Jagim's equation should not be used in high-level male athletes.


Unilateral laterothoracic exanthema with coincident evidence of Epstein Barr virus reactivation: exploration of a possible link.
Unilateral laterothoracic exanthem (ULE) was first described in 1962 in the United States and comprehensively elaborated in 1992. Although ULE most commonly occurs in children, ULE can occur in adults. ULE may or may not be preceded by a viral prodrome and is marked by coalescing erythematous papules predominately on one side of the body. ULE usually lasts 4-6 weeks but can last as little as 2 weeks. It has inconsistently been linked to viral infection, in particular parvovirus B-19. I note ULE in an adult with concurrent reactivation of Epstein Barr virus (EBV) that lasted 4 weeks. The role of the reactivation of EBV in human disease and ULE is explored.


Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints.
We examined whether cerebral metabolic rates for glucose (CMRglc) on 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) and cerebrospinal fluid (CSF) markers of Alzheimer's disease (AD) are altered in cognitively normal apolipoprotein E (ApoE) E4 carriers with subjective memory complaints (SMC). Twenty-eight middle-aged normal subjects (NL) were examined, including 13 E4 carriers (E4+; 6 with SMC [SMC+] and 7 without SMC [SMC-]) and 15 noncarriers (E4-; 7 SMC+ and 8 SMC-). Subjects received an FDG-PET scan and a lumbar puncture to measure CSF total (T-Tau) and hyperphosphorylated tau(231) (P-Tau), 40 and 42 amino acid forms of beta-amyloid (Abeta40 and Abeta42), and F(2)-isoprostane (IP). As compared with E4-, E4+ subjects showed decreased CMRglc in AD-related brain regions and associated higher CSF IP, P-Tau, T-Tau, and P-Tau/Abeta42 levels (p's < .05). As compared with SMC-, SMC+ subjects showed reduced parietotemporal and parahippocampal gyrus (PHG) CMRglc. A significant ApoE by SMC status interaction was found, with the E4+/SMC+ showing the lowest PHG CMRglc and the highest CSF IP, P-Tau, and P-Tau/Abeta42 levels as compared with all other subgroups (p's < or = .05). The combination of CSF and CMRglc measures significantly improved the accuracy of either measures alone in discriminating ApoE groups (86% accuracy, odds ratio [OR] = 4.1, p < .001) and E4+/SMC+ from all other subgroups (86% accuracy, OR = 3.7, p = .005). Parahippocampal gyrus CMRglc was the most accurate discriminator of SMC groups (75% accuracy, OR = 2.4, p < .001). Normal E4 carriers with SMC show altered AD-related CSF and FDG-PET measures. Longitudinal studies are needed to assess whether these brain abnormalities foreshadow clinical decline.


Multi-class, multi-residue determination of 132 veterinary drugs in milk by magnetic solid-phase extraction based on magnetic hypercrosslinked polystyrene prior to their determination by high-performance liquid chromatography-tandem mass spectrometry.
A quantitative multi-class multi-residue analytical method was developed for the determination of veterinary drugs in milk by high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS). A total of 132 veterinary drugs investigated belonged to almost 15 classes including sulfonamides, β-lactams, tetracyclines, quinolones, macrolides, nitrofurans, nitroimidazoles, phenicols, lincosamides, pleuromutilins, macrocyclic lactones, quinoxaline antibiotics, benzimidazoles, anthelmintics, coccidiostats and some others. A magnetic solid-phase extraction procedure was developed using magnetic hypercrosslinked polystyrene (HCP/Fe3O4) for the sample preparation prior to HPLC-MS/MS without deproteinization step. The results indicated recoveries of 85-107% for 14 sulfonamides, 85-120% for 13 β-lactams, 89-115% for 4 tetracyclines, 82-119% for 14 quinolones, 82-115% for 8 macrolides, 97-109% for 4 nitrofurans, 84-115% for 10 nitroimidazoles, 89-114% for 3 phenicols, 86-111% for 3 lincosamides, 97-102% for 2 pleuromutilins, 72-88% for 4 macrocyclic lactones, 87-104% for 4 quinoxaline antibiotics, 76-119% for 21 benzimidazoles, 79-115% for 12 anthelmintics, 81-118% for 12 coccidiostats and 75-119 % for 5 unclassified drugs, with relative standard deviations (RSDs) of less than 20%, and the LOQs ranged from 0.05 to 1 μg kg-1. This methodology was then applied to field-collected real milk samples and trace levels of some veterinary drugs were detected.


Multidrug tolerance of biofilms and persister cells.
Bacterial populations produce a small number of dormant persister cells that exhibit multidrug tolerance. All resistance mechanisms do essentially the same thing: prevent the antibiotic from hitting a target. By contrast, tolerance apparently works by shutting down the targets. Bactericidal antibiotics kill bacteria by corrupting their targets, rather than merely inhibiting them. Shutting down the targets then protects from killing. The number of persisters in a growing population of bacteria rises at mid-log and reaches a maximum of approximately 1% at stationary state. Similarly, slow-growing biofilms produce substantial numbers of persisters. The ability of a biofilm to limit the access of the immune system components, and the ability of persisters to sustain an antibiotic attack could then account for the recalcitrance of such infections in vivo and for their relapsing nature. Isolation of Escherichia coli persisters by lysing a population or by sorting GFP-expressing cells with diminished translation allowed to obtain a gene expression profile. The profile indicated downregulated biosynthetic pathways, consistent with their dormant nature, and indicated overexpression of toxin/antitoxin (TA) modules. Stochastic overexpression of toxins that inhibit essential functions such as translation may contribute to persister formation. Ectopic expression of RelE, MazF, and HipA toxins produced multidrug tolerant cells. Apart from TA modules, glpD and plsB were identified as potential persister genes by overexpression cloning of a genomic library and selection for antibiotic tolerance. Yeast Candida albicans forms recalcitrant biofilm infections that are tolerant to antibiotics, similarly to bacterial biofilms. C. albicans biofilms produce multidrug tolerant persisters that are not mutants, but rather phenotypic variants of the wild type. Unlike bacterial persisters, however, C. albicans persisters were only observed in a biofilm, but not in a planktonic stationary population. Identification of persister genes opens the way to a rational design of anti-biofilm therapy. Combination of a conventional antibiotic with a compound inhibiting persister formation or maintenance may produce an effective therapeutic. Other approaches to the problem include sterile-surface materials, prodrug antibiotics, and cyclical application of conventional antimicrobials.


Prognostic indicator for the resection of liver metastasis of colorectal cancer.
We investigated the predictive indicator for a good prognosis of surgical resection for liver metastasis of colorectal cancer. Between 1990 and 2009 at our institute, 117 patients underwent 132 hepatic resections for liver metastasis of colorectal cancer. The clinical, pathological, and outcome parameters affecting their prognoses were analyzed. The extent of the liver metastases was subdivided according to the Japanese Classification of Colorectal Carcinoma (JCCRC), and the patients were classified into different grades based on the JCCRC classification and the status of the nodal involvement of the primary tumor. The median survival time (MST) of the 117 patients was 58 months, and the actuarial survival rates at 1, 3, and 5 years were 92.3, 60.0, and 46.1 %, respectively. A multivariate analysis revealed that the JCCRC Grade classification was an independent prognostic indicator (Grade A vs. B vs. C: MST, 72 vs. 41 vs. 23 months; 5-year survival, 59.0 vs. 38.6 vs. 0 %: p < 0.0001). Our findings indicate that the JCCRC Grade classification for liver metastasis of colorectal cancer is a significant prognostic indicator and may be useful for making decisions regarding the treatment of liver metastasis.


Pediatric, adolescent, and young-adult nutrition issues in IDDM.
Although insulin is life sustaining for patients with insulin-dependent diabetes mellitus (IDDM), the meal plan is of critical importance for avoiding hyperglycemia, preventing hypoglycemia, and maintaining metabolic balance. Consistency, timing, composition, and caloric content of food intake and physical activity, age, sex, growth, and pubertal status alter meal-plan needs. Self-monitoring of blood glucose should be used to individualize the meal plan. The general American Diabetes Association recommendations suggest that 50-65% of total calories be from carbohydrates from foods with a lower glycemic index and/or high fiber content. Protein should contribute 12-20% of total calories and fat less than 30%, with less than 10% saturated fat and less than 300 mg/day cholesterol. More severe fat restriction should be considered in individuals with persistent lipid abnormalities when compared with sex- and age-adjusted values. Calories should be sufficient for growth and development, with growth data obtained several times a year and plotted on standardized weight, height, and velocity charts. Blood pressure should be similarly plotted on age- and sex-standardized curves.(ABSTRACT TRUNCATED AT 250 WORDS)


Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis-a proof of principle and exploratory trial: is dose tapering practical in good responders?
RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response. We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0-6) patients were randomized to control (constant TNFi) or two experimental groups (tapering TNFi by 33 or 66%). Subsequently (months 6-12) control subjects were randomized to taper TNFi by 33 or 66%. Disease flares (DAS28 increasing ⩾0.6 with at least one additional swollen joint) were the primary outcome. Two hundred and forty-four patients were screened, 103 randomized and 97 treated. In months 0-6 there were 8/50 (16%) flares in controls, 3/26 (12%) with 33% tapering and 6/21 (29%) with 66% tapering. Multivariate Cox analysis showed time to flare was unchanged with 33% tapering but was reduced with 66% tapering compared with controls (adjusted hazard ratio 2.81, 95% CI: 0.99, 7.94; P = 0.051). Analysing all tapered patients after controls were re-randomized (months 6-12) showed differences between groups: there were 6/48 (13%) flares with 33% tapering and 14/39 (36%) with 66% tapering. Multivariate Cox analysis showed 66% tapering reduced time to flare (adjusted hazard ratio 3.47, 95% CI: 1.26, 9.58; P = 0.016). Tapering TNFi by 33% has no impact on disease flares and appears practical in patients in sustained remission and low disease activity states. EudraCT, https://www.clinicaltrialsregister.eu, 2010-020738-24; ISRCTN registry, https://www.isrctn.com, 28955701.


Optimization of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of HIV capsid assembly inhibitors 2: structure-activity relationships (SAR) of the C3-phenyl moiety.
Detailed structure-activity relationships of the C3-phenyl moiety that allow for the optimization of antiviral potency of a series of 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione inhibitors of HIV capsid (CA) assembly are described. Combination of favorable substitutions gave additive SAR and allowed for the identification of the most potent compound in the series, analog 27. Productive SAR also transferred to the benzotriazepine and spirobenzodiazepine scaffolds, providing a solution to the labile stereocenter at the C3 position. The molecular basis of how compound 27 inhibits mature CA assembly is rationalized using high-resolution structural information. Our understanding of how compound 27 may inhibit immature Gag assembly is also discussed.


Single drug therapy for intractable epilepsy.
Single drug therapy with either phenytoin or primidone resulted in complete seizure control in 11 of 35 patients (31%) referred to an epilepsy clinic for treatment of uncontrolled chronic epilepsy with complex-partial seizures. Complete seizure control was associated with an increase in the mean plasma concentrations from 14 micrograms/ml to 23 micrograms/ml phenytoin and from 34 micrograms/ml to 40 micrograms/ml phenobarbitone with no change in the antiepileptic drug. Insufficiently low plasma concentrations of less than 11 micrograms/ml phenytoin or phenobarbitone were measured at the first visit in 14 patients (40%). Non-compliance was admitted by eight patients (23%). Optimum single drug therapy is of considerable clinical value in intractable epilepsy with complex-partial seizures.


Radiography of microcalcifications in stereotaxic mammary core biopsy specimens.
To describe the technique of specimen radiography in stereotaxically guided core biopsies and evaluate its role in detection and diagnosis of microcalcifications in breast tissue. Specimens from 361 stereotaxic breast core biopsies of 72 nonpalpable lesions with mammographic evidence of microcalcifications were obtained from 65 patients. Specimens were placed in saline on microscope slides and radiographed. Microcalcifications were detected radiographically in 146 of 361 (40%) cores. If calcifications were present on specimen radiographs, histologic detection of these calcifications was made in 114 of 146 (78%) specimens, and diagnosis was made in 118 of 146 (81%). If calcifications were not present on specimen radiographs, histologic detection was obtained in 27 of 215 (13%) specimens and specific diagnosis in 81 of 215 (38%). Specimen radiography should be routinely performed in stereotaxic core biopsies of breast microcalcifications to ensure appropriate tissue has been obtained and to direct pathologic diagnosis of the tissue specimens.


Review of Studies Evaluating Effectiveness of Risk Minimization Measures Assessed by the European Medicines Agency Between 2016 and 2021.
The European Medicines Agency (EMA) supervises medicines' safe and effective use throughout the product's life cycle by, for example, monitoring the implementation of risk minimization measures (RMMs). Limited information is available on factors associated with effectiveness of RMMs. This study reviews post-authorization safety studies (PASS) evaluating the effectiveness of RMMs assessed by the Pharmacovigilance Risk Assessment Committee (PRAC) between 2016 and 2021. PASS assessment reports finalized by PRAC between January 1, 2016, and December 31, 2021, were compiled from non-public EMA databases and PASS characteristics were extracted. Of the 93 PASS included, 62.4% aimed to measure healthcare professionals' awareness, knowledge, and behavior regarding RMMs. There were 67.7% of the 93 PASS that used primary data, 24.7% used secondary data sources, and 7.5% used both. A cross-sectional study design was most frequently applied (77.4%), followed by a cohort study design (29.0%). Nearly 40% of the included PASS did not render a conclusion on RMM effectiveness. Of the 60% that did render a conclusion, 82.1% were deemed effective. Only minor differences in characteristics were found when stratified by outcome (i.e., effective RMM, ineffective RMM, and no conclusion on RMM effectiveness). To conclude, 4 out of 10 PASS assessing impact of RMMs did not render a conclusion on RMM effectiveness. No clear differences in PASS characteristics were found in relation to their outcomes, indicating that additional research is needed to understand better the underlying reasons for PASS being inconclusive.


Accuracy of Ultrasound Jugular Venous Pressure Height in Predicting Central Venous Congestion.
Assessment of volume status through the estimation of central venous pressure (CVP) is integral in the care of heart failure (HF). Bedside assessment is limited by obesity, variation in physical examination skills, and expertise in ultrasonography. To validate the accuracy of quantitative and qualitative point-of-care ultrasonography assessment of jugular venous pressure (JVP) in predicting elevated CVP. Prospective observational study using convenience sampling. 2 U.S. academic hospitals. Adult patients undergoing right heart catheterization between 5 February 2019 and 1 March 2021. Estimation of the JVP height by handheld ultrasound device (uJVP), JVP by traditional physical examination, and qualitative presence of a distended uJVP in the upright position (upright-uJVP) was done before invasive measurements. Receiver-operating characteristic analysis of the uJVP was compared with invasive hemodynamics. In 100 participants undergoing right heart catheterization for HF indications (mean age, 59.6 years; 44% with preserved ejection fraction), the uJVP in a reclined position accurately predicted elevated right atrial pressure (RAP) (>10 mm Hg), with an area under the curve of 0.84. A positive uJVP in the upright position was 94.6% specific for predicting elevated RAP. Limited examiners, only 2 centers, and convenience sampling. Point-of-care ultrasonography assessment of the uJVP is feasible, reproducible, and accurately predictive of elevated CVPs in patients undergoing right heart catheterization. Further investigation of clinical application of ultrasound-measured JVP seems warranted. None.


Investigation of parasitic and viral pathogens in mussels (Mytilus galloprovincialis) in the Gulf of Izmir, Turkey.
To investigate Microsporidia spp. parasite, hepatitis A virus (HAV), and norovirus (NoV) contamination in mussels collected from 8 stations in the inner, middle, and outer regions of the Gulf of Izmir. In this cross-sectional study carried out between August 2009 and September 2010 in the Gulf of Izmir, Turkey, 15 mussels collected from each of the stations each season were pooled and homogenized to create a single representative sample. Thirty representative samples were available for analysis. Direct polymerase chain reaction (PCR), RT-nested PCR, and RT-booster PCR were used to investigate the pathogens. The mussels were negative for Microsporidia spp., but 8 (26.7%) samples analyzed were positive for HAV and 9 (30%) were positive for NoV. Excluding Foca and Gediz, viral contamination was detected in all of the stations sampled. Our results suggest that viral contamination is present in mussels in the Gulf of Izmir and may pose a potential threat to human health in the region. Necessary measures should be taken to prevent future illness due to these pathogens.


Weight and its relationship to adolescent perceptions of their providers (WRAP): a qualitative and quantitative assessment of teen weight-related preferences and concerns.
To examine the relationship of body weight to satisfaction with care in adolescents, and to obtain qualitative data on preferences for general and weight-related medical care in normal weight and overweight adolescents. The Weight and its Relationship to Adolescent Perceptions of their Providers survey, a 4-page questionnaire containing previously validated satisfaction scales and open-ended qualitative questions regarding health care preferences, was administered to 62 severely overweight (body mass index [BMI] 38.9 +/- 8.4 kg/m2) and 29 normal weight (BMI 22.5 +/- 4.0 kg/m2) adolescents (age 13.9 +/- 1.7 years; 57% female; 50% Caucasian, 47% African-American, 3% Hispanic). The affective subscale of the medical satisfaction scale was negatively correlated with BMI standard deviation score (r = -.22, p < .05). Multiple regression models predicting affective satisfaction with medical care included BMI standard deviation score; however, continuity with provider appeared to be the strongest independent predictor of affective satisfaction. Fifty-five percent of participants identified their mother as the person they felt most comfortable talking with about weight, although 68% believed their provider knew the most about healthy eating. "Overweight" was identified by 47% of participants as the preferred term for heavy teens. Seventy-nine percent of overweight adolescents stated their health care provider discussed their weight with them; however, only 41% of overweight adolescents desired to discuss their weight. Compared to normal-weight adolescents, overweight teens were more likely to report that their provider raised topics of weight (p < .001), diet (p < .01), and exercise (p < .01) at their last physical, and were more likely to report that they would have liked their provider to discuss diet and exercise (both p < .05). Ten percent of overweight teens expressed concerns regarding the public location of their provider's office scale. Satisfaction with affective aspects of the provider-patient relationship is negatively correlated with BMI standard deviation score. Length of experience with one's provider is also a strong predictor of teen satisfaction with their medical care. Teens prefer the term "overweight" for those with high body weight. Sensitivity to confidentiality, privacy, and embarrassment regarding physical examination and weight are important for teen satisfaction.


Midazolam and flumazenil in neuroanaesthesia.
Of the numerous benzodiazepines currently available, only a few are used in anaesthetic practice. Midazolam is utilised as a premedicant, sedative, and an induction agent and produces minimal depression of ventilation or of the cardiovascular system. The anticonvulsant activity is similar to that of diazepam. In neuroanaesthesia midazolam may be an acceptable alternative to other intravenous induction agents like barbiturates or etomidate in patients with compromised intracranial compliance. Midazolam produces dose-related reductions in cerebral blood flow and cerebral oxygen consumption. However, midazolam does not necessarily prevent increases in intracranial pressure during induction of anaesthesia. In the electroencephalogram (EEG) midazolam produces a reduction in alpha-activity, an increase in theta-delta-activity and low-voltage beta-activity. Midazolam like other benzodiazepines does not affect early components of auditory and somatosensory evoked responses, whereas late cortical responses may be suppressed. Flumazenil, a specific benzodiazepine antagonist, has been demonstrated to be effective in reversing benzodiazepine-induced sedation. In the EEG midazolam-induced changes vanish almost instantaneously. Flumazenil is also effective in restoring the amplitudes of cortical auditory and somatosensory evoked responses. However, as has been demonstrated in head-injured patients and animal experiments after incomplete cerebral ischaemia, increases in cerebral blood flow and intracranial pressure cannot be excluded after flumazenil administration. When utilising flumazenil for wake-up procedures in midazolam-sedated patients with pathological intracranial compliance, flumazenil has to be titrated very carefully in low doses over prolonged periods.


Predictive factors for nodal recurrence in differentiated thyroid cancers.
Differentiated thyroid carcinoma usually has a good prognosis. Primary treatment is surgery, followed by radioactive iodine ablation based on risk stratification. The incidence of local and distant recurrence is 30%. Recurrence can be managed surgically or with multiple cycles of radioactive iodine ablation. There are multiple risk factors for structural disease recurrence proposed by the American Thyroid Association. In this study, we attempted to study the risk factors of structural recurrence in differentiated carcinoma thyroid and the pattern of recurrence in patients with node negative thyroid cancer who underwent total thyroidectomy. This study selected a retrospective cohort of 1498 patients with differentiated thyroid cancer: out of these, 137 patients who presented after thyroidectomy with cervical nodal recurrence from January 2017 to December 2020 were included. The risk factors for central and lateral lymph node metastasis were analysed by univariate and multivariate analyses, including age, gender, T-stage, extrathyroidal extension, multifocality and high-risk variants. In addition, the presence of TERT/BRAF mutations was studied as a risk factor for central and lateral nodal recurrence. Out of 1498 patients, 137 who fit the inclusion criteria were analysed. Majority were female (73%); mean age was 43.1 years. Lateral compartment neck nodal recurrence was more common (84%), while isolated central compartment nodal recurrence occurred only in 16%. Most recurrences were seen in the first 1 year (23.3%) or after 10 years post-total thyroidectomy (35.7%). On univariate variate analysis, multifocality, extrathyroidal extension and high-risk variants stage were significant factors for nodal recurrence. However, on multivariate analysis for lateral compartment recurrence, multifocality, extrathyroidal extension and age were found to be significant. On multivariate analysis, multifocality, extrathyroidal extension and presence of high-risk variants were significant predictors of central compartment nodal metastasis. ROC curve analysis showed AUC for ETE (AUC-0.795), multifocality (AUC-0.860), presence of high-risk variants (AUC-0.727) and T-stage (AUC-0.771) as sensitive predictive factors for central compartment. 69 percent patients with very early recurrences (<6 month) had TERT/BRAF V600 E mutations. In our study, we have noted extrathyroidal extension and multifocality as significant risk factors for nodal recurrence. BRAF and TERT mutations are associated with aggressive clinical course and early recurrences. There is limited role of prophylactic central compartment node dissection.


Decreasing lower extremity junctional and perineal injury from explosive blast with a pelvic protection system.
Lower extremity junctional injuries due to explosive blasts are among the most lethal sustained on the battlefield. To help reduce the effects of junctional and perineal trauma from this injury mechanism, a tiered Pelvic Protection System (PPS) was fielded during the war in Afghanistan. Thirty-six patients with known PPS status who sustained traumatic above knee amputations, with and without perineal injuries, were identified from an operative amputation registry in Helmand Province, Afghanistan, spanning a 12-month period. In Group 1 patients with above knee amputations who wore some tier of the PPS system, 47% (8 of 17) sustained junctional/perineal injuries. Of the patients in Group 2 who wore no PPS, 68% (13 of 19) sustained perineal injuries associated with proximal amputations. Overall, these differences were statistically significant (p = 0.0115). Use of a PPS may reduce the risk of having severe perineal and lower extremity junctional injury in service members sustaining traumatic above knee amputations from an explosive blast.


Treatment with low doses of cabergoline is not associated with increased prevalence of cardiac valve regurgitation in patients with hyperprolactinaemia.
Dopamine agonists have been reported to increase the risk of cardiac valve regurgitation in patients with Parkinson's disease. However, it is unknown whether these drugs might be harmful for patients with hyperprolactinaemia (HyperPRL). The aim of the study was to evaluate whether HyperPRL patients treated with dopamine agonists had a higher prevalence of cardiac valves regurgitation than that of general population. One hundred consecutive patients (79 women, 21 men, mean age 41 +/- 13 years) with HyperPRL during treatment with cabergoline were enrolled in an observational case-control study and compared with 100 matched normal subjects (controls). Valve regurgitation was assessed by echocardiography according to the American Society of Echocardiography recommendations. Seven HyperPRL patients (7%) and six controls (6%) had moderate (grade 3) regurgitation in any valve (p = 0.980). All were asymptomatic and had no signs of cardiac disease. Mean duration of cabergoline treatment was 67 +/- 39 months (range: 3-199 months). Mean cumulative dose of cabergoline was 279 +/- 301 mg (range: 15-1327 mg). Moderate valve regurgitation was not associated with the duration of treatment (p = 0.359), with cumulative dose of cabergoline (p = 0.173), with age (p = 0.281), with previous treatment with bromocriptine (p = 0.673) or previous adenomectomy (p = 0.497) in patients with HyperPRL. In conclusion, treatment with cabergoline was not associated with increased prevalence of cardiac valves regurgitation in patients with HyperPRL. Mean cumulative dose of cabergoline was lower in patients with HyperPRL than that reported to be deleterious for patients with Parkinson's disease: hence, longer follow-up is necessary, particularly in patients receiving weekly doses > 3 mg.


Calcium peroxide and freezing co-pretreatment enhancing short-chain fatty acids production from waste activated sludge towards carbon-neutral sludge treatment.
Short-chain fatty acids (SCFAs) recovery through anaerobic fermentation is a promising technology to achieve carbon-neutral in waste activated sludge (WAS) management. After 0.15 g CaO2/g volatile suspended solids (VSS) addition and three-cycle freezing co-pretreatments, the maximal SCFAs production of 438.5 mg COD/g VSS was achieved within 4 days fermentation, and more than 70 % of SCFAs was composed of acetate and propionate, which achieved a higher level than reported in previous studies. Mechanism explorations elucidated that co-pretreatment triggered sludge solubilization, promoting the release of biodegradable organics, providing more biodegradable substrates for SCFAs generation. Further microbial community analysis indicated that the abundances of hydrolytic microorganisms and acidogens were enriched, whereas methanogens were inhibited. Besides, environmental analysis suggested that co-pretreatment could achieve carbon reduction benefits of 0.116-0.291 ton CO2/ton WAS, demonstrating its huge carbon-neutral potential benefits.


Cystic fibrosis related diabetes: Medical management.
Cystic Fibrosis Related Diabetes Mellitus (CFRD) drives excess pulmonary morbidity and mortality in patients with cystic fibrosis (CF). The recommended treatment is insulin therapy. Insulin therapy in CF should be customized to the specific patient. CF patients typically require intensive insulin regimens such as multiple daily injections or insulin pump therapy, but frequently require lower doses than in type 1 diabetes mellitus. Patients with CF may also need insulin to cover intravenous or enteral feedings. Pre-diabetic glycaemic abnormalities are also associated with clinical decline in cystic fibrosis prior to the diagnosis of CFRD, however, whether and how this should be treated is not fully determined. There is also interest, but inadequate data regarding other treatments besides insulin (i.e., oral medications) for treatment of pre-diabetes or CFRD. CFTR potentiator and corrector therapy has yet to demonstrate an effect on the rate of CFRD, but may improve insulin secretion. There is great opportunity for further research to better understand when and how best to treat glycaemic abnormalities in cystic fibrosis.


Unexplained gastrointestinal bleed due to arteriobiliary fistula after percutaneous liver biopsy.
We represent a case of a 54-year-old male who presented to the emergency department with right upper quadrant abdominal pain and melena three weeks after percutaneous liver biopsy. He was found to have anemia secondary to an upper gastrointestinal hemorrhage, unresponsive to multiple blood transfusions. Angiography later revealed an arteriobiliary fistula with contrast extravasation entering the duodenum. The fistula was successfully embolized and the patient was discharged without complication. This report demonstrates the importance in considering a vascular intrahepatic fistula in patients with right upper quadrant abdominal pain after remote liver biopsy.


Amperometric glucose biosensor based on gold-deposited polyvinylferrocene film on Pt electrode.
The preparations and performances of the novel amperometric biosensors for glucose based on immobilized glucose oxidase (GOD) on modified Pt electrodes are described. Two types of modified electrodes for the enzyme immobilization were used in this study, polyvinylferrocene (PVF) coated Pt electrode and gold deposited PVF coated Pt electrode. A simple method for the immobilization of GOD enzyme on the modified electrodes was described. The enzyme electrodes developed in this study were called as PVF-GOD enzyme electrode and PVF-Au-GOD enzyme electrode, respectively. The amperometric responses of the enzyme electrodes were measured at constant potential, which was due to the electrooxidation of enzymatically produced H2O2. The electrocatalytic effects of the polymer, PVF, and the gold particles towards the electrooxidation of the enzymatically generated H2O2 offers sensitive and selective monitoring of glucose. The biosensor based on PVF-Au-GOD electrode has 6.6 times larger maximum current, 3.8 times higher sensitivity and 1.6 times larger linear working portion than those of the biosensor based on PVF-GOD electrode. The effects of the applied potential, the thickness of the polymeric film, the amount of the immobilized enzyme, pH, the amount of the deposited Au, temperature and substrate concentration on the responses of the biosensors were investigated. The optimum pH was found to be pH 7.4 at 25 degrees C. Finally the effects of interferents, stability of the biosensors and applicability to serum analysis of the biosensor were also investigated.


The effects of plantar fasciitis and pain on plantar pressure distribution of recreational runners.
Plantar fasciitis is the third most frequent injury in runners. Despite its high prevalence, its pathogenesis remains inconclusive. The literature reports overload as the basic mechanism for its development. However, the way that these plantar loads are distributed on the foot surface of runners with plantar fasciitis and the effects of pain on this mechanical factor has not yet been investigated. Therefore, the aim of this study was to evaluate and compare the plantar pressure distributions during running in runners with symptom or history of plantar fasciitis and runners without the disease. Forty-five recreational runners with plantar fasciitis (30 symptomatic and 15 with previous history of the disease) and 60 runners without plantar fasciitis (control group) were evaluated. Pain was assessed by a visual analogue scale. All runners were evaluated by means of the Pedar system insoles during running forty meters at a speed of 12(5%) km/h, using standard sport footwear. Two-way ANOVAS were employed to investigate the main and interaction effects between groups and plantar areas. No interaction effects were found for any of the investigated variables: peak pressure (P = 0.61), contact area (P = 0.38), contact time (P = 0.91), and the pressure-time integral (P = 0.50). These findings indicated that the patterns of plantar pressure distribution were not affected in recreational runners with plantar fasciitis when compared to control runners. Pain also did not interfere with the dynamic patterns of the plantar pressure distributions.


Clinical characteristics and outcome in muscular sarcoidosis: a retrospective cohort study and literature review.
We evaluated the clinical features and treatment response of patients with muscular sarcoidosis. A retrospective cohort of 12 patients showed muscle weakness in 11 and myalgia in seven. One had focal myositis. Four had a negative medical history for sarcoidosis. Muscle imaging showed muscle edema in all and replacement of muscle tissue by fat in half of patients. Muscle biopsy showed non-caseating granulomas in six of nine patients and inflammation without granulomas in three. None of the muscle biopsies showed features of inclusion body myositis. Imaging in three patients without muscle biopsy showed focal intramuscular masses or a 'tiger man' appearance typical for muscular sarcoidosis. Treatment consisted of glucocorticoids in 11, additional methotrexate or azathioprine in seven and infliximab in two patients. Half of the patients had symptoms leading to substantial disability (modified Rankin scale score >1) at last follow-up. A literature review of articles describing more than one muscular sarcoidosis patient published in the last 25 years identified 153 additional patients. We found muscular sarcoidosis to be a rare and often disabling disease which may be recognized by typical muscle imaging characteristics and add focal myositis to the muscular phenotypes of sarcoidosis.


The emergence of a change in the prevalence of preeclampsia in a tertiary maternity unit (2004-2016).
Pre-eclampsia (PET) affects 2-3% of all pregnancies, rising to 5-7% in nulliparous women. This study aimed to investigate the prevalence of PET over a 13-year period. A retrospective review was performed over a 13-year period (2004-2016) via interrogation of the annual clinical reports of The Rotunda Hospital, Dublin. There was a fall in the overall incidence of PET (nulliparous and multiparous), from a peak of 3.8% in 2007 to 1.5% in 2015. Comparing the first and second halves of the study time-period this decrease was statistically significant (p < .0001). In nulliparous women, the thirteen-year mean was 4.4% for the study period, with a similar observed reduction from a peak of 5.3% in 2005 to a trough of 2.4% in 2015. In our institution, we have shown a decrease in preeclampsia rates over a 13-year period. While the reason for this trend remains unclear, a similar trend has been observed in another tertiary unit and additional research is required to explain the etiology behind these observations.


The combination of Helicobacter pylori- and cytotoxin-associated gene-A seropositivity in relation to the risk of myocardial infarction in middle-aged Japanese: The Japan Public Health Center-based study.
Limited evidence is available concerning the impact of the combination of Helicobacter pylori- (H. pylori) and cytotoxin-associated gene-A (CagA)-positivity on the risk of myocardial infarction (MI) and stroke, particularly in Asian populations, in which the prevalence of H. pylori infection is high. A prospective, nested case-control study was conducted to examine the association between H. pylori and CagA and risk of MI and stroke within a cohort of 29,876 men and women aged 40-69 years with no history of heart disease, stroke or cancer. Participants completed a risk factor survey and donated blood samples between 1990 and 1994. Systematic cardiovascular surveillance was performed through 2002. One control for each stroke case and two controls for each MI case were matched by sex, age, date of blood sampling, time since last meal and study location. During the follow-up period, there were 600 strokes and 106 MIs. H. pylori-IgG positivity was not associated with the risk of MI, while CagA positivity tended to be associated with it (OR = 1.72, 95%CI: 0.91-3.26, p = 0.10). We found no association between H. pylori or CagA and risk of stroke. H. pylori infection was not significantly associated with risk of MI and stroke among middle-aged Japanese. However, CagA positivity tended to be associated with MI.


Emicizumab prophylaxis in patients with haemophilia A with and without inhibitors.
Emicizumab is a bispecific monoclonal antibody that mimics factor VIII (FVIII) by binding to factors IXa and X to promote hemostasis in haemophilia A (HA) and HA with inhibitors (HA-I). As emicizumab differs biochemically from FVIII, there is interest in its real-world haemostatic efficacy. To describe real-world patient experience with emicizumab by retrospective chart review. We reviewed medical records of patients cared for at the Hemophilia Center of Western PA, who initiated emicizumab following its licensure, and on whom bleeding events and factor use were available. Comparisons between groups were done by Student's t test for continuous data and by chi-square or Fisher's exact test for discrete data. A total of 42 patients whose charts were reviewed included 18 (42.9%) with HA and 24 (52.1%) with HA-I. Groups were similar in age, 17 (40.5%) <18 years, race, and haemophilia severity, and initiated weekly subcutaneous emicizumab 1.5 mg/kg, following 4-week induction. Fourteen (33.3%) experienced at least one breakthrough bleed, of which 11 (44.0%) were joint bleeds, with an annualized bleed rate (ABR), 0.9 ± 0.3, not different between groups, P = .251. Surgical procedures were performed in 10 (23.8%), of whom 4 (40.0%) had postoperative bleeding and one developed postoperative thrombosis in association with FEIBA despite emicizumab discontinuation 1 month preoperatively. Local skin reactions occurred in three and headache in one. Overall, 85.0% of those who rated their health indicated it was improved. Despite breakthrough bleeds and postoperative thrombosis associated with emicizumab, most HA and HA-I experienced improved health.


Stenting of Variant Left Carotid Artery Using Brachial Artery Approach in a Patient with Unusual Type of Bovine Aortic Arch.
Bovine aortic arch is the most frequently encountered variation in human aortic arch branching. A 63-year-old Asian male presented with symptomatic severe stenosis of left carotid artery originating from the brachiocephalic trunk. Selective engagement to the left carotid artery was unsuccessful using transfemoral approach. We reported on a successful left carotid artery stenting case using right brachial artery approach in a bovine aortic arch. This paper is worthy of reporting in terms of guiding physicians for interventional procedures in these types of challenging cases.


Cell-based and stem-cell-based treatments for spinal cord injury: evidence from clinical trials.
Spinal cord injury is a severely disabling neurological condition leading to impaired mobility, pain, and autonomic dysfunction. Most often, a single traumatic event, such as a traffic or recreational accident, leads to primary spinal cord damage through compression and laceration, followed by secondary damage consisting of inflammation and ischaemia, and culminating in substantial tissue loss. Patients need appropriate timely surgical and critical care, followed by neurorehabilitation to facilitate neuronal reorganisation and functional compensation. Although some neurological function might be regained, most patients with initially complete lesions have severe, irreversible neurological impairment. Cell-based and stem-cell-based therapies are recognised as promising candidates to promote functional recovery. However, no trials of these therapies in patients have yet provided reproducible evidence for clinical efficacy, challenged by small effect sizes, low immune suppression, and low sensitivity study designs. Nevertheless, in the past decade, clinical trials have shown the feasibility and long-term safety of cell transplantation into the injured spinal cord. This crucial milestone has paved the way to consider refinements and combined therapies, such as the use of biomaterials to augment the effects of cell transplantation. In the future, emerging cell types, scaffolding, and cell engineering might improve cell survival, integration, and therapeutic efficiency.


Relationship between plasma lipoprotein (a), apolipoprotein (a) phenotypes, and other coronary heart disease risk factors in a Melbourne South Asian population.
High plasma lipoprotein(a) [Lp(a)] level is a strong and important risk factor for cardiovascular disease (CVD). Small-sized apolipoprotein(a) [apo(a)] isoforms (F, B, S1, and S2) are inversely correlated with the high levels of Lp(a) in plasma and significantly associated with CVD. Although the effects of apo(a) phenotypes and various risk factors on Lp(a) status in South Asian population may have been studied in other countries, there are no reports involving these risk factors in Australia. Factors contributing to variation in Lp(a) were surveyed in 402 (216 males and 186 females) South Asian Melburnians. There was a negative relationship between low alcohol beer per day and Lp(a) in men (P < 0.05). Approximately 21% of the variance of Lp(a) concentration in men and 6% in women were explained by age. Age was positively associated with Lp(a) concentrations in men but negatively in women. The most commonly occurring phenotype was apo(a) S3. In this phenotype, Lp(a) concentrations ranged from non-detectable to 811 mg/l. After adjusting for age, an inverse correlation was observed between Lp(a) concentration and apo(a) phenotypes (P < 0.01). Although Lp(a) has been reported to be genetically determined, there are clearly other factors contributing to variations in Lp(a) concentrations in a South Asian population.


Cisplatin, doxorubicin, cyclophosphamide, and etoposide combination chemotherapy for small-cell lung cancer.
Because of potential synergistic interactions, we added 25 mg/m2 i.v. cisplatin (P) 25 given on days 1-5 to the combination of 45 mg/m2 i.v. doxorubicin (A) given on day 1, 800 mg/m2 i.v. cyclophosphamide (C) given on day 1, and 50 mg/m2 i.v. etoposide (E) given on days 1-5. The resulting PACE regimen was given every 21 days for the first three courses and then every 28 days for the next five courses. PACE was used in two trials: the first, for both limited and extensive disease, was conducted at the University of Maryland Cancer Center and North Shore University Hospital; and the second, for extensive disease, was carried out as a Cancer and Leukemia Group B pilot study. Chest irradiation was not used. Prophylactic cranial irradiation at a dose of 3,000 cGy was given to all patients achieving a complete response (CR). A total of 33 subjects were entered in the first study; 8 of the 15 (53%) presenting with limited disease and 7 of the 18 (39%) exhibiting extensive disease achieved a CR. A partial response (PR) was obtained in 27% and 33% of cases, respectively. Of the 34 patients entered in the second study, 25 were eligible; 8 (32%) achieved a CR and 6 (24%) showed a PR. Toxicity was severe in both studies, including greater than 90% severe or life-threatening leukopenia and thrombocytopenia. Serial creatinine-clearance evaluations in the first study indicated progressive deterioration, which required discontinuation of the cisplatin before the planned completion of treatment in most cases. Since the response rate was no higher than the historic data reported for the three-drug ACE combination and because the toxicity was severe, the studies were stopped and patients were followed for survival. After a follow-up period of greater than 6 years, the median survival was 24 months for limited disease, with 33% and 27% of the patients being alive at 3 and 6.5 years, respectively. The median survival for extensive disease was 15 and 11 months in the first and second studies, respectively. These pilot studies suggest that the addition of cisplatin may augment the activity of the ACE regimen, but at the cost of severe toxicity. Further studies seem warranted if the myelotoxicity can be better controlled.


Standardising measurement of tumour vascularity by imaging: recommendations for ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography.
This review analyses the need for, and likely impact of, four subsequent papers which discuss the importance of standardisation of ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) when assessing tumour vascularity. This is particularly important when measuring the vascular effects of therapeutic agents in oncological research and practice. As imaging inexorably moves from the subjective interpretative art-form of the past into its modern role as a fully fledged objective scientific discipline, it is incumbent on all radiologists to understand the need for strict adherence to perceived best practice when evaluating lesions as part of trials. Indeed trials may only be funded by pharmaceutical companies and other grant-giving bodies if rigorous adherence to imaging protocols and quality assurance is in place. Key Points • Various imaging methods can now robustly assess tumour vascular support. • US, CT, MRI and PET are increasingly used to assess tumour vascularity. • These techniques have reached technical maturity for use in therapeutic oncological trials. • Consensus guidelines about using these techniques in assessing tumour vascularity are introduced. • Image acquisition protocols and quality assurance must be established for large trials.


Variations in serum metabolites in response to season, cyclicity, and pregnancy in estrus-synchronized Damascus goats.
The current study was carried out to determine the changes in serum electrolytes, liver enzymes, and hormones during breeding and non-breeding seasons in estrus-synchronized goats. Forty goats (n = 40) were synchronized by inserting the sponges intravaginally for 12 days; PMSG and PGF2α were injected on day of sponge removal. Blood samples were collected from the goats at the time of sponges insertion (day -12), estrus day (day 0), and at 15 day after sponge withdrawal (day 15). The blood samples were analyzed for glucose, cholesterol (CHO), aspartate aminotransferase (AST), alanine aminotransferase (ALT), thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4) and progesterone (P4), calcium (Ca), phosphate (PO4), magnesium (Mg), sodium (Na), potassium (K), and chlorine (Cl) levels. Repeated measurements ANOVA of general linear model were used as statistical model. The results showed that seasons have an effect (p < 0.05) on glucose, Ca, Na, K, Cl, CHO, T3, and T4 levels. There was an effect (p < 0.05) of cyclicity only on P4 level. Whereas, nonpregnant, or goats carrying singlet and twin fetuses have shown variation (p < 0.05) in glucose, Ca, and P4 levels. Although, the correlations existed between different serum metabolites but strong correlations (p < 0.05) were observed either between Ca and Na or T3 and T4. In conclusion, the serum electrolytes and liver enzymes are correlated with hormones during the different seasons, pregnancy status, and fecundity. In recommendation, the results of the study could be as managemental tool to monitor the reproductive activity across seasons and to maintain pregnancy carrying twining in goat breeds.


Feasibility and safety of deep sedation with propofol and remifentanil in spontaneous breathing during endoscopic retrograde cholangiopancreatography: an observational prospective study.
Endoscopic retrograde cholangiopancreatography (ERCP) is an interventional procedure that requires deep sedation or general anaesthesia. The purpose of this prospective observational study was to assess the feasibility and safety of deep sedation in ERCP to maintain spontaneous breathing. This is a single-centre observational prospective cohort study conducted in a tertiary referral university hospital. All consecutive patients who needed sedation or general anaesthesia for ERCP were included from January 2021 to June 2021. Deep sedation was achieved and maintained by continuous infusion of an association of propofol and remifentanil. The primary endpoint was to assess the prevalence of major anaesthesia-related complications, such as arrhythmias, hypotension, gas exchange dysfunction, and vomiting (safety endpoint). Secondary endpoints were: (a) to assess the prevalence of signs of an insufficient level of sedation, such as movement, cough, and hiccups (feasibility endpoint): (b) time needed to achieve the target level of sedation and for recovery from anaesthesia. In order to do so we collect the following parameters: peripheral oxygen saturation, fraction of inspired oxygen, noninvasive systemic blood pressure, heart rate, number of breaths per minute, neurological functions with the use of the bispectral index to determine depth of anaesthesia, and partially exhaustive CO2 end pressure to continuously assess the ventilatory status. The collected data were analysed by several tests: Shapiro-Wilk, Student's t, Tuckey post-hoc, Wilcoxon rank-sum and Kruskall-Wallis ran. Statistical analysis was performed using Stata/BE 17.0 (StataCorp LLC). 114 patients were enroled. Eight patients were excluded because they did not meet the inclusion criteria. We found that all patients were hemodynamically stable: intraoperative mean systolic blood pressure was 139,23 mmHg, mean arterial pressure was on average 106,66 mmHg, mean heart rate was 74,471 bpm. The mean time to achieve the target level of sedation was 63 s, while the mean time for the awakening after having stopped drug infusion was 92 s. During ERCP, deep sedation and analgesia using the association of propofol and remifentanil and maintaining spontaneous breathing are safe and feasible, allowing for a safe and quick recovery from anaesthesia.


Lymphokines and bacteria, that induce tumoricidal activity, trigger a different secretory response in macrophages.
The abilities of various macrophage-activating agents to trigger tumoricidal activity and/or the secretion of prostaglandin E2 (PGE2), interleukin 6 (IL 6) and transforming growth factor beta (TGF beta) in bone marrow-derived mononuclear phagocytes (BMM phi) in vitro were comparatively assessed. Induction of tumoricidal activity by lymphokines, that is only short-lived, was not associated with enhanced secretion of these activities by BMM phi; in contrast, incubation with heat-killed facultative intracellular bacteria resulted in persisting tumoricidal activity and in marked enhancement of the secretion of IL 6 and PGE2, but not of TGF beta activity. These findings support the concept that the pattern of the secretory response induced in macrophages by lymphokines differs from that triggered by bacteria and that the rapid decay of lymphokine-induced tumoricidal activity is not due to autocrine macrophage deactivation mediated by one of these agents alone.


Tau fibrils induce glial inflammation and neuropathology via TLR2 in Alzheimer's disease-related mouse models.
Glial activation and inflammation coincide with neurofibrillary tangle (NFT) formation in neurons. However, the mechanism behind the interaction between tau fibrils and glia is poorly understood. Here, we found that tau preformed fibrils (PFFs) caused induction of inflammation in microglia by specifically activating the TLR2/MyD88, but not the TLR4/MyD88, pathway. Accordingly, the WT TLR2-interacting domain of MyD88 (wtTIDM) peptide inhibited tau PFF-induced activation of the TLR2/MyD88/NF-κB pathway, resulting in reduced inflammation. Nasal administration of wtTIDM in P301S tau-expressing PS19 mice was found to inhibit gliosis and inflammatory markers, as well as to reduce pathogenic tau in the hippocampus, resulting in improved cognitive behavior in PS19 mice. The inhibitory effect of wtTIDM on tau pathology was absent in PS19 mice lacking TLR2, reinforcing the essential involvement of TLR2 in wtTIDM-mediated effects in vivo. Studying the mechanism further, we found that the tau promoter harbored a potential NF-κB-binding site and that proinflammatory molecules increased transcription of tau in neurons via NF-κB. These results suggest that tau-induced neuroinflammation and neuropathology require TLR2 and that neuroinflammation directly upregulates tau in neurons via NF-κB, highlighting a direct connection between inflammation and tauopathy.


Molecular characterization of methicillin-resistant and methicillin-sensitive Staphylococcus aureus isolates from human milk samples in Brazil.
Human milk is the best nutrient for infants. The donor human milk is stored in a milk bank before pasteurization. However, the human milk is not sterile and could be colonized with different types of bacteria. Many studies have shown S. aureus to be the most prevalent potential pathogen detected in human milk. This study characterized 22 methicillin-resistant and methicillin-sensitive Staphylococcus aureus isolates from raw human milk for the presence of virulence genes and agr type. Moreover, the genotypic as identified characterization was realized. The presence of virulence genes sei, seg, sec, seh, and etb was identified in resistant and sensitive strains. We observed the predominance of agr type II. The presence of SCCmec IV (67%, 4/6) and V (33%, 2/6) characterized resistant strains as CA-MRSA. Endemic lineages detected (ST1635/CC5-t002, ST5/CC5-t002, ST72/CC5-t126, ST1/CC1-t127, ST45/CC45-t065, and ST398/t1451) could be related to epidemic clones, such as USA800/ST5, USA700/ST72, USA400/ST1, USA600/ST45, and ST398. This study made it possible to understand the characteristics of virulence and clonality of some strains that circulate in breast milk in our region. The discovery of human milk colonization by MSSA and MRSA strains with molecular characteristics similar to infectious clones spread globally demonstrates the importance of monitoring strains that can spread and cause serious infections.


T2* map at cardiac MRI reveals incidental hepatic and cardiac iron overload.
The purpose of this study was to assess the diagnostic capabilities of cardiac magnetic resonance (CMR) T2* mapping in detecting incidental hepatic and cardiac iron overload. Patients with various clinical indications for CMR examination were consecutively included at a single center from January 2019 to April 2023. All patients underwent T2* mapping at 1.5 T in a single mid-ventricular short-axis as part of a comprehensive routine CMR protocol. T2* measurements were performed of the heart (using a region-of-interest in the interventricular septum) and the liver, categorized according to the severity of iron overload. The degree of cardiac iron overload was categorized as mild (15 ms < T2* < 20 ms), moderate (10 ms < T2* < 15 ms) and severe (T2* < 10 ms). The degree of hepatic iron overload was categorized as mild (4 ms < T2* < 8 ms), moderate (2 ms < T2* < 4 ms), severe (T2* < 2 ms). Image quality and inter-reader agreement were assessed using intraclass correlation coefficient (ICC). CMR examinations from 614 patients (374 men, 240 women) with a mean age of 50 ± 18 (standard deviation) years were fully evaluable. A total of 24/614 patients (3.9%) demonstrated incidental hepatic iron overload; of these, 22/614 patients (3.6%) had mild hepatic iron overload, and 2/614 patients (0.3%) had moderate hepatic iron overload. Seven out of 614 patients (1.1%) had incidental cardiac iron overload; of these, 5/614 patients (0.8%) had mild iron overload, 1/614 patients (0.2%) had moderate iron overload, and 1/614 patients (0.2%) had severe iron overload. Good to excellent inter-reader agreement was observed for the assessment of T2* values (ICC, 0.90 for heart [95% confidence interval: 0.88-0.91]; ICC, 0.91 for liver [95% confidence interval: 0.89-0.92]). Analysis of standard CMR T2* maps detects incidental cardiac and hepatic iron overload in 1.1% and 3.9% of patients, respectively, which may have implications for further patient management. Therefore, despite an overall low number of incidental abnormal findings, T2* imaging may be included in a standardized comprehensive CMR protocol.


Lactobacillus rhamnosus GG aggravates vascular calcification in chronic kidney disease: A potential role for extracellular vesicles.
Lactobacillus rhamnosus GG (LGG) is a probiotic with great promise in future clinical application, which can significantly promote bone formation. However, the effect of LGG on CKD-related vascular calcification is unclear. In this study, we aimed to investigate the effect of LGG on CKD-related vascular calcification. After 2 weeks of 5/6 nephrectomy, CKD rats received a special diet (4 % calcium and 1.8 % phosphate) combined with 1,25-dihydroxyvitamin D3 to induce vascular calcification. Meanwhile, CKD rats in the LGG group were gavaged orally with LGG (1 × 109 CFU bacteria/day). 16S RNA amplicon sequencing was performed to analyze the effect of LGG treatment on gut microbiota composition. Furthermore, differential ultracentrifugation was utilized to extract EVs. The effects of EVs on vascular calcification were evaluated in rat VSMCs, rat aortic rings, and CKD rat calcification models. In this study, vascular calcification was assessed by microcomputed tomography analysis, alizarin red staining, calcium content determination, and the expression of osteogenic transcription factors RUNX2 and BMP2. LGG remarkably aggravated vascular calcification. LGG supplementation significantly altered gut microbiota composition in CKD rats, particularly increasing Lactobacillus. Interestingly, EVs presented a significant promoting effect on the development of calcification. Finally, mechanistic analysis proved that EVs aggravated vascular calcification through PI3K/AKT signaling. These results do not support the supplementation of LGG in CKD-associated vascular calcification patients. Our study presented a fresh perspective on LGG with potential risks and adverse effects. CKD patients should use specific probiotic strains cautiously.


Age-related increase in liver retinyl palmitate. Relationship to lipofuscin.
Lipofuscin is a general term assigned to fluorescent material that accumulates in cells as they age. It is apparent from this study that the fluorescent intensity of detergent-solubilized liver from Fisher-344 rats increased as a function of age. The fluorophore responsible for this increase was extracted with methanol and could be resolved from other cellular components when the methanol extracts were chromatographed over a reverse phase column. This compound was identified as retinyl palmitate and was found to increase throughout the entire life of the Fisher-344 rat (2-24 months), from a value of 0.26-1.77 mg/g of liver. In addition, the results presented here demonstrate that concentration, time between extraction and analysis, exposure to light, and degree of purity affect the observed fluorescent properties of retinyl palmitate. These factors affect many fluorophores and are likely to be, at least in part, responsible for the multiplicity of reported properties of lipofuscin. As has been reported for lipofuscin, retinyl palmitate accumulates in intracellular granules and exhibits fluorescence between 450 and 600 nm. Due to these similarities, the relationship between retinyl palmitate and lipofuscin warrants further investigation.


Structural covariance in the cortex of very preterm adolescents: a voxel-based morphometry study.
On the basis of findings in normative samples that different cortical brain regions covary in gray matter volume, most likely as a result of mutually trophic influences during cortical development, we aimed to study whether patterns of covariation in regional gray matter, i.e., structural covariance, differed between adolescents who were born very preterm and full-term controls. Optimized voxel-based morphometry was used to study structural magnetic resonance imaging scans from 218 very preterm adolescents (gestational age <33 weeks) and 127 controls at 14-15 years of age. Local gray matter volumes were obtained for 18 regions of interest involved in sensorimotor and higher-order cognitive functions. These were then used to predict local volumes in the remaining areas of the cortex, with total gray matter volume, age and gender used as confounding variables. Very preterm adolescents compared with controls demonstrated differential (i.e., both increased and decreased) structural covariance between medial, frontal and cingulate gyri, caudate nucleus, thalamus, primary visual cortex, cerebellum and several other cortical and subcortical regions of the cortex. These findings support previous research indicating that preterm birth is associated with altered cortical development, and suggest that developmental changes in one brain region may result in a cascade of alterations in multiple regions.