Structurally diverse zinc(II) complexes containing tripodal tetradentate phenoxido-amines with promising antiproliferative effects.

Structurally diverse zinc(II) complexes with tripodal tetradentate phenolic-amines of variable substituents in the phenol and amine moieties were synthesized and thoroughly characterized. The two dinuclear [Zn2(L1)2](ClO4)2·MeOH (1), [Zn2(L2)2](ClO4)2 (2), and four mononuclear [Zn(L3)(H2O)]·MeOH (3), [Zn(L4)] (4), [Zn(L5)] (5) and [Zn(L6)] (6) complexes revealed distorted octahedral, trigonal-bipyramidal or tetrahedral geometries. The free HL1 and H2L3-6 ligands, and complexes 1-6 were evaluated for in vitro cytotoxicity against human cancer cell lines (A2780, A2780R, PC-3 and 22Rv1) and normal healthy MRC-5 cells. Overall results revealed high-to-moderate cytotoxicity (with the best IC50 values for complex 6 ranging from 2.4 to 4.5 µM), which is however, significantly higher than that of the reference drug cisplatin. The moderately active complexes 1-4 showed considerable selectivity on A2780 cells (IC50 ≈ 16.3-19.5 µM) over MRC-5 ones (with IC50 >50 µM for 1, 2 and 4, and with IC50 >25 µM for 3). The complexes 1, 2, and 6 and the ligand H2L6 were chosen for subsequent deeper biological evaluations. Their time-resolved cellular uptake and other cellular effects in A2780 cells were studied, such as cell cycle profile, intracellular ROS production, induction of apoptosis and activation of caspases 3/7. Complexes 1 and 2 caused significant G0/G1 cell cycle arrest in A2780 cells and antioxidant effects at normal conditions. They showed only limited effects on cellular processes connected with cytotoxicity, i.e. induction of apoptosis, depletion of mitochondrial membrane potential, and autophagy. These findings can be at least partly attributed to the low ability of the complexes to enter the A2780 cells and the depression of metabolic activity of the target cancer cells.

Undergraduate medical student perceptions and learning outcomes related to anatomy training using Thiel- and ethanol-glycerin-embalmed tissues.

Anatomical dissection is known to serve as an integral tool in teaching gross anatomy, including postgraduate training. A variety of embalming techniques exist, resulting in different haptic and optical tissue properties. This study aimed to objectify learning outcomes and medical student perceptions related to the use of two widely used embalming techniques, namely Thiel and ethanol-glycerin embalming. Between 2020 and 2022, first- and second-year medical students enrolled in the course on topographic anatomy participated in this study. Objective structured practical examinations were carried out for the head, neck, thorax, abdomen, pelvis, and extremity regions following regional dissection just before the oral examinations began. Six to ten numbered tags were marked in prosections of each region in Thiel- and ethanol-glycerin-embalmed specimens. Following the examinations, the students were surveyed regarding the suitability of the two embalming techniques with respect to preservation, colorfastness, tissue pliability, and the suitability in preparing for their anatomy examinations. Consistently higher scores were achieved for the thoracic and abdominal regions in ethanol-glycerin-embalmed specimens when compared to Thiel. No benefit was found for Thiel-embalmed upper or lower extremities. Tissues embalmed with ethanol-glycerin were rated higher for preservation and suitability to achieve the learning objectives, tissue pliability was rated higher for Thiel-embalmed tissues. Ethanol-glycerin embalming appears to offer certain advantages for undergraduate students in recognizing visceral structures, which may align with students' ideas on tissue suitability for their learning. Consequently, the benefits reported for Thiel embalming for postgraduate study unlikely reflect its suitability for novices.

Magnetostructural Properties of Some Doubly-Bridged Phenoxido Copper(II) Complexes.

Three new tripod tetradentate phenolate-amines (H2L1, H2L4 and H2L9), together with seven more already related published ligands, were synthesized, and characterized. With these ligands, two new dinuclear doubly-bridged-phenoxido copper(II) complexes (3, 4), and six more complexes (1, 2, 5-8), a new trinuclear complex (9) with an alternative doubly-bridged-phenoxido and -methoxido, as well as the 1D polymer (10) were synthesized, and their molecular structures were characterized by spectroscopic methods and X-ray single crystal crystallography. The Cu(II) centers in these complexes exhibit distorted square-pyramidal arrangement in 1-4, mixed square pyramidal and square planar in 5, 6, and 9, and distorted octahedral (5+1) arrangements in 7 and 8. The temperature dependence magnetic susceptibility study over the temperature range 2-300 K revealed moderate-relatively strong antiferromagnetic coupling (AF) (|J| = 289-145 cm-1) in complexes 1-6, weak-moderate AF (|J| = 59 cm-1) in the trinuclear complex 9, but weak AF interactions (|J| = 3.6 & 4.6 cm-1) were obtained in 7 and 8. No correlation was found between the exchange coupling J and the geometrical structural parameters of the four-membered Cu2O2 rings.

Dinuclear doubly bridged phenoxido copper(II) complexes as efficient anticancer agents.

Two cationic [Cu2(L1-2)2](ClO4)2 (1, 2), and four neutral doubly bridged-phenoxido-copper(II) complexes [Cu2(L3-4)2] (3, 4) and [Cu2(L5-6)2(H2O)]‧2H2O (5, 6) as well as 1D polymeric catena-[Cu(L7)] (7), where HL1-2 and H2L3-7 represent tripodal tetradentate pyridyl or aliphatic-amino groups based 2,4-disubstituted phenolates, were synthesized and thoroughly characterized by various spectroscopic methods and single crystal X-ray analysis. The molecular structures of the complexes exhibited diverse geometrical environments around the central Cu(II) atoms. The in vitro antiproliferative activity of the isolated complexes and selected parent free ligands were screened against some human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, MCF-7). The most promising cytotoxicity against cancer cells were obtained for 1-6, while complex 6 was found as the best performing as compared to the reference drug cisplatin. The cytotoxicity study of complex 6 was therefore extended to wider variety of cancer cell lines (HOS, A549, PANC-1, CaCo2, HeLa) and results revealed its significant cytotoxicity on all investigated human cancer cells. The cell uptake study showed that cytotoxicity of 6 (3 µM concentration and 24 h of incubation) against A2780 cells was almost independent from the intracellular levels of copper. The effect of complexes 4, 6 and 7 on cell cycle of A2780 cells indicates that the mechanism of action in these complexes is not only different from that of cisplatin but also different among them. Complex 7 was able to induce apoptosis in A2780 cells, while complexes 4 and 6 did not and on the other hand, they showed considerable effect on autophagy induction and there are some clues that these complexes were able to induce cuproptosis in A2780 cells.

On the added benefit of virtual anatomy for dissection-based skills.

Technological approaches deploying three-dimensional visualization to integrate virtual anatomy are increasingly used to provide medical students with state-of-the-art teaching. It is unclear to date to which extent virtual anatomy may help replace the dissection course. Medical students of Johannes Kepler University attend both a dissection and a virtual anatomy course. This virtual anatomy course is based on Cinematic Rendering and radiological imaging and teaches anatomy and pathology. This study aims to substantiate student benefits achieved from this merged teaching approach. Following their dissection course, 120 second-year students took part in objective structured practical examinations (OSPE) conducted on human specimens prior to and following a course on Cinematic Rendering virtual anatomy. Likert-based and open-ended surveys were conducted to evaluate student perceptions of both courses and their utility. Virtual anatomy teaching was found to be unrelated to improvements in student's ability to identify anatomical structures in anatomical prosections, yielding only a 1.5% increase in the OSPE score. While the students rated the dissection course as being more important and impactful, the virtual anatomy course helped them display the learning content in a more comprehensible and clinically applicable way. It is likely that Cinematic Rendering-based virtual anatomy affects knowledge gain in domains other than the recognition of anatomical structures in anatomical prosections. These findings underline students' preference for the pedagogic strategy of the dissection course and for blending this classical approach with novel developments like Cinematic Rendering, thus preparing future doctors for their clinical work.

Should statistical analysis of bond-strength data include or exclude cohesive failures?

OBJECTIVES: The aim was to investigate shear bond strengths and failure modes of four self-etch bonding agents to bovine dentin and enamel and to compare evaluation of data sets with or without exclusion of cohesive failure specimens. METHODS: Composite-cylinders were bonded perpendicularly to bovine dentin and enamel surfaces. Shear-strengths were measured 24 h post-bonding of: Scotchbond Universal® (SBU, 3 M), OptiBond™ XTR (OBXTR, Kerr), OptiBond™ universal (OBU, KaVo-Kerr) and Prime & Bond active® (PBA, Dentsply-Sirona). Analysis of overall data was made via a linear mixed-model. This was repeated after exclusion of specimens associated with cohesive failures. RESULTS: When both adhesive and cohesive failures were considered, OBU and OBXTR showed comparable dentin and enamel bond strengths, whereas lower strengths were found on enamel for SBU (p < 0.001) and PBA (p = 0.015). For OBXTR higher shear strengths were measured for specimens associated with cohesive failures. When cohesive failures were excluded, the majority of shear bond strengths of adhesive failure specimens were only slightly different from overall results. However, uniquely with OBXTR dramatically lower shear bond strengths were found for dentin substrate. SIGNIFICANCE: After exclusion of cases with cohesive failures OBXTR adhesive fell behind other materials in the sequence of average shear strengths. This did not reflect the actual performance of the material. Therefore, in statistical analysis we do not recommend exclusion of data based on a specific fracture mode.

Insights into the Spin Dynamics of Mononuclear Cerium(III) Single-Molecule Magnets.

Four novel CeIII mononuclear complexes of formulas [Ce(ntfa)3(MeOH)2] (1), [Ce(ntfa)3(5,5'-Me2bipy)] (2), [Ce(ntfa)3(terpy)] (3), and [Ce(ntfa)3(bipy)2] (4), where ntfa = 4,4,4-trifluoro-1-(naphthalen-2-yl)butane-1,3-dionato, 5,5'-Me2bipy = 5,5'-dimethyl-2,2'-dipyridyl, terpy = 2,2':6',2″-terpyridine, and bipy = 2,2'-bipyridine, have been synthesized and structurally characterized with CeIII displaying coordination numbers of 8, 8, 9, and 10, respectively. Magnetic measurements indicate that all the complexes show a field-induced single-ion magnet behavior under a small applied dc field. The magnetic analysis shows the relevance of the different spin relaxation mechanisms in the magnetic relaxation of the CeIII compounds, with special emphasis on the local-mode process. Multiconfigurational calculations were also performed to get more information on the axiality of the compounds.

Validation Study for Non-Invasive Prediction of IDH Mutation Status in Patients with Glioma Using In Vivo 1H-Magnetic Resonance Spectroscopy and Machine Learning.

The isocitrate dehydrogenase (IDH) mutation status is an indispensable prerequisite for diagnosis of glioma (astrocytoma and oligodendroglioma) according to the WHO classification of brain tumors 2021 and is a potential therapeutic target. Usually, immunohistochemistry followed by sequencing of tumor tissue is performed for this purpose. In clinical routine, however, non-invasive determination of IDH mutation status is desirable in cases where tumor biopsy is not possible and for monitoring neuro-oncological therapies. In a previous publication, we presented reliable prediction of IDH mutation status employing proton magnetic resonance spectroscopy (1H-MRS) on a 3.0 Tesla (T) scanner and machine learning in a prospective cohort of 34 glioma patients. Here, we validated this approach in an independent cohort of 67 patients, for which 1H-MR spectra were acquired at 1.5 T between 2002 and 2007, using the same data analysis approach. Despite different technical conditions, a sensitivity of 82.6% (95% CI, 61.2-95.1%) and a specificity of 72.7% (95% CI, 57.2-85.0%) could be achieved. We concluded that our 1H-MRS based approach can be established in a routine clinical setting with affordable effort and time, independent of technical conditions employed. Therefore, the method provides a non-invasive tool for determining IDH status that is well-applicable in an everyday clinical setting.

Role of Energy Metabolism and Mitochondrial Function in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic recurring inflammation of the intestine which can be debilitating for those with intractable disease. However, the etiopathogenesis of inflammatory bowel disorders remains to be solved. The hypothesis that mitochondrial dysfunction is a crucial factor in the disease process is being validated by an increasing number of recent studies. Thus mitochondrial alteration in conjunction with previously identified genetic predisposition, changes in the immune response, altered gut microbiota, and environmental factors (eg, diet, smoking, and lifestyle) are all posited to contribute to IBD. The implicated factors seem to affect mitochondrial function or are influenced by mitochondrial dysfunction, which explains many of the hallmarks of the disease. This review summarizes the results of studies reporting links between mitochondria and IBD that were available on PubMed through March 2021. The aim of this review is to give an overview of the current understanding of the role of mitochondria in the pathogenesis of IBD.

We address the effect of energy metabolism and mitochondrial function on the pathogenesis of inflammatory bowel disease. Because many studies on this topic have been published recently, it is important to give an overview of the results of that work.

Magnetic and Luminescence Properties of 8-Coordinate Holmium(III) Complexes Containing 4,4,4-Trifluoro-1-Phenyl- and 1-(Naphthalen-2-yl)-1,3-Butanedionates.

A new series of mononuclear Ho3+ complexes derived from the ß-diketonate anions: 4,4,4-trifluoro-1-phenyl-1,3-butanedioneate (btfa-) and 4,4,4-trifuoro-1-(naphthalen-2-yl)-1,3-butanedionate (ntfa-) have been synthesized, [Ho(btfa)3(H2O)2] (1a), [Ho(ntfa)3(MeOH)2] (1b), (1), [Ho(btfa)3(phen)] (2), [Ho(btfa)3(bipy)] (3), [Ho(btfa)3(di-tbubipy)] (4), [Ho(ntfa)3(Me2bipy)] (5), and [Ho(ntfa)3(bipy)] (6), where phen is 1,10-phenantroline, bipy is 2,2'-bipyridyl, di-tbubipy is 4,4'-di-tert-butyl-2,2'-bipyridyl, and Me2bipy is 4,4'-dimethyl-2,2'-bipyridyl. These compounds have been characterized by elemental microanalysis and infrared spectroscopy as well as single-crystal X-ray difraction for 2-6. The central Ho3+ ions in these compounds display coordination number 8. The luminescence-emission properties of the pyridyl adducts 2-6 display a strong characteristic band in the visible region at 661 nm and a series of bands in the NIR region (excitation wavelengths (λex) of 367 nm for 2-4 and 380 nm for 5 and 6). The magnetic properties of the complexes revealed magnetically uncoupled Ho3+ compounds with no field-induced, single-molecule magnet (SMMs).

Expression of Oxidative Phosphorylation Complexes and Mitochondrial Mass in Pediatric and Adult Inflammatory Bowel Disease.

INTRODUCTION: Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a multifactorial intestinal disorder but its precise etiology remains elusive. As the cells of the intestinal mucosa have high energy demands, mitochondria may play a role in IBD pathogenesis. The present study is aimed at evaluating the expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes in IBD. Material and Methods. 286 intestinal biopsy samples from the terminal ileum, ascending colon, and rectum from 124 probands (34 CD, 33 UC, and 57 controls) were stained immunohistochemically for all five OXPHOS complexes and the voltage-dependent anion-selective channel 1 protein (VDAC1 or porin). Expression levels were compared in multivariate models including disease stage (CD and UC compared to controls) and age (pediatric/adult). RESULTS: Analysis of the terminal ileum of CD patients revealed a significant reduction of complex II compared to controls, and a trend to lower levels was evident for VDAC1 and the other OXPHOS complexes except complex III. A similar pattern was found in the rectum of UC patients: VDAC1, complex I, complex II, and complex IV were all significantly reduced, and complex III and V showed a trend to lower levels. Reductions were more prominent in older patients compared to pediatric patients and more marked in UC than CD. CONCLUSION: A reduced mitochondrial mass is present in UC and CD compared to controls. This is potentially a result of alterations of mitochondrial biogenesis or mitophagy. Reductions were more pronounced in older patients compared to pediatric patients, and more prominent in UC than CD. Complex I and II are more severely compromised than the other OXPHOS complexes. This has potential therapeutic implications, since treatments boosting biogenesis or influencing mitophagy could be beneficial for IBD treatment. Additionally, substances specifically stimulating complex I activity should be tested in IBD treatment.

Cost-effectiveness of home-based care of febrile neutropenia in children with cancer.

INTRODUCTION: Home-based treatment of febrile neutropenia (FN) in children with cancer with oral or intravenous antibiotics is safe and effective. There are limited data on the economic impact of this model of care. We evaluated the cost-effectiveness of implementing an FN programme, incorporating home-based intravenous antibiotics for carefully selected patients, in a tertiary paediatric hospital. METHODS: A decision analytic model was constructed to compare costs and outcomes of the home-based FN programme, with usual in-hospital treatment with intravenous antibiotics. The programme included a clinical decision rule to stratify patients by risk for severe infection and home-based eligibility criteria using disease, chemotherapy and patient-level factors. Health outcomes (quality of life) and probabilities of FN risk classification and home-based eligibility were based on prospectively collected data between 2017 and 2019. Patient-level costs were extracted from hospital administrative records. Cost-effectiveness was expressed as the incremental cost per quality-adjusted life year (QALY). FINDINGS: The mean health care cost of home-based FN treatment in low-risk patients was Australian dollars (A$) 7765 per patient compared to A$20,396 for in-hospital treatment (mean difference A$12,632 [95% CI: 12,496-12,767]). Overall, the home-based FN programme was the dominant strategy, being more effective (0.0011 QALY [95% CI: 0.0011-0.0012]) and less costly. Results of the model were most sensitive to proportion of children eligible for home-based care programme. CONCLUSION: Compared to in-hospital FN care, the home-based FN programme is cost-effective, with savings arising from cheaper cost of caring for children at home. These savings could increase as more patients eligible for home-based care are included in the programme.

Imaging of exercise-induced spinal remodeling in elite rowers.

OBJECTIVES: As in-vivo knowledge of training-induced remodeling of intervertebral discs (IVD) is scarce, this study assessed how lumbar IVDs change as a function of long-term training in elite athletes and age-matched controls using compositional Magnetic Resonance Imaging (MRI). DESIGN: Prospective case-control study. METHODS: Prospectively, lumbar spines of 17 elite rowers (ERs) of the German national rowing team (mean age: 23.9 ±â€¯3.3 years) were imaged on a clinical 3.0 T MRI scanner. ERs were imaged twice during the annual training cycle, i.e., at training intensive preseason preparations (t0) and 6 months later during post-competition recovery (t1). Controls (n = 22, mean age: 26.3 ±â€¯1.9 years) were imaged once at corresponding time points (t0: n = 11; t1: n = 11). Segment-wise, the glycosaminoglycan (GAG) content of lumbar IVDs (n = 195) was determined using glycosaminoglycan chemical exchange saturation transfer (gagCEST). Linear mixed models were set up to assess the influence of cohort and other variables on GAG content. RESULTS: During preseason, IVD GAG values of ERs were significantly higher than those of controls (ERs(t0): 2.58 ±â€¯0.27% (mean ±â€¯standard deviations); controls(t0): 1.43 ±â€¯0.36%; p ≤ 0.001), while during post-competition recovery, such differences were not present anymore (ERs(t1): 2.11 ±â€¯0.18%; controls(t1): 1.89 ±â€¯0.24%; p = 0.362). CONCLUSIONS: Professional elite-level rowing is transiently associated with significantly higher gagCEST values, which indicate increased lumbar IVD-GAG content and strong remodeling effects in response to training. Beyond professional rowing, core-strengthening full-body exercise may help to enhance the resilience of the lumbar spine as a potential therapeutic target in treating back pain.

Asociación de los grados de movilidad de la articulación atlanto-occipital con la clasificación de Cormack- Lehane como predictores de una vía aérea pediátrica difícil en pacientes de 0 a 12 años de edad en el Hospital Municipal Boliviano Holandés, 2017 / Association of the degrees of mobility of the atlanto-occipital joint with the Cormack-Lehane classification as predictors of a difficult pediatric airway in patients aged 0 to 12 years at the" Municipal Boliviano Holandés" Hospital, 2017

OBJETIVO. Determinar la asociación que existe entre las valoraciones de la articulación atlantooccipital durante la valoración preanestésica y la valoración del Cormack Lehane durante la intubación para predecir una vía aérea difícil en el paciente pediátrico de 0 a 12 años de edad que ingresaron a quirófano del Hospital Municipal Boliviano Holandés en los meses de agosto a octubre de la Gestión 2017. MATERIAL Y METODOS. Es un diseño observacional descriptivo de corte transversal, en 70 pacientes de 0 a 12 años de edad que siguiendo criterios estrictos de inclusión se evaluó la clasificación de vía aérea difícil pediátrica analizando la concordancia entre la asociación de la valoración de la articulación atlantooccipital con la escala de Cormack-Lehane. RESULTADOS. Se evaluaron pacientes entre 0 a 12 años, la Escala de Bellhouse Dore encontrada fue Grado I 39%, Grado III 29%, Grado II 24% y Grado IV 8% y el Cormack Lehane encontrado es grado I 39%, grado III 29%, grado II 24% y el grado IV 8%. La asociación de ambas escalas determinó como predictor de vía aérea normal al 63%, potencialmente difícil 29% y vía aérea difícil 8%. CONCLUSIÓN. Existe asociación entre las valoraciones de la articulación atlantooccipital durante la valoración preanestesica y la valoración del Cormack Lehane durante la intubación como predictor de una vía aérea difícil en el paciente pediátrico de 0 a 12 años de edad.

OBJECTIVE. To determine the association that exists between the assessments of the atlanto-occipital joint during the preanesthetic assessment and the assessment of the Cormack Lehane during intubation to predict a difficult airway in pediatric patients aged 0 to 12 who were admitted to the Municipal Boliviano Holandés Hospital in the months of August to October of the Management 2017. MATERIAL AND METHODS. It is an observational descriptive crosssectional design, in 70 patients from 0 to 12 years of age who, following strict inclusion criteria, evaluated the classification of pediatric difficult airway, analyzing the concordance between the association of the atlanto-occipital joint assessment with the Cormack-Lehane scale. RESULTS. Patients between 0 to 12 years old were evaluated, the Bellhouse Dore Scale found was Grade I 39%, Grade III 29%, Grade II 24% and Grade IV 8% and the Cormack Lehane found is grade I 39%, grade III 29 %, grade II 24% and grade IV 8%. The association of both scales determined a 63% normal airway as a predictor, 29% potentially difficult and 8% difficult airway. CONCLUSION. There is an association between the assessments of the atlanto-occipital joint during the pre-anesthetic assessment and the assessment of the Cormack Lehane during intubation as a predictor of a difficult airway in pediatric patients 0 to 12 years of age.

Identification of potent anticancer copper(ii) complexes containing tripodal bis[2-ethyl-di(3,5-dialkyl-1H-pyrazol-1-yl)]amine moiety.

A series of heteroleptic copper(ii) complexes of the composition [Cu(L1-5)Cl]X, where X = ClO4 and/or PF6 and [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl))-(6-methyl-(2-pyridylmethyl))]amine (L1), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl))-(3,4-dimethoxy-(2-pyridylmethyl))]amine (L2), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl)-(2-quinolymethyl)]amine (L3), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazolyl)-(di(3,5-dimethyl-1H-pyrazol-1-yl-methyl))]amine (L4) and [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl)-(5-methyl-3-phenyl-1H-pyrazol-1-yl-methyl)]amine (L5), were prepared and thoroughly characterized including single-crystal X-ray diffraction technique. The in vitro cytotoxicity of complexes against A2780, A2780R, HOS and MCF-7 human cancer cell lines was evaluated using the MTT test. The results revealed that complexes [Cu(L1)Cl]PF6 (1-PF6), [Cu(L2)Cl]ClO4 (2-ClO4) and [Cu(L3)Cl]PF6 (3-PF6) are the most effective, with IC50 values ranging from 1.4 to 6.3 µM, thus exceeding the cytotoxic potential of metallodrug cisplatin (IC50 values ranging from 29.9 to 82.0 µM). The complexes [Cu(L4)Cl]PF6 (4-PF6) and [Cu(L5)Cl]PF6 (5-PF6) showed only moderate cytotoxicity against A2780, with IC50 = 53.6 µM, and 33.8 µM, respectively. The cell cycle profile, time-resolved cellular uptake, interactions with small sulfur-containing biomolecules (cysteine and glutathione), intracellular ROS production, induction of apoptosis and activation of caspases 3/7 were also evaluated in the case of the selected complexes. It has been found that the best performing complexes 1 and 2 cause cell arrest in the G2/M phase and induce apoptosis via the increase in production of ROS, dominantly due to the overproduction of superoxide.

Blood group AB increases risk for surgical necrotizing enterocolitis and focal intestinal perforation in preterm infants with very low birth weight.

Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are two of the most common emergencies of the gastrointestinal tract in preterm infants with very low birth weight (VLBW, birth weight < 1500 g). Identification of risk factors among these children is crucial for earlier diagnosis and prompt intervention. In this study, we investigated a relationship between ABO blood groups and the risk for surgical NEC/FIP. We genotyped the ABO locus (rs8176746 and rs8176719) in VLBW infants enrolled in a prospective, population-based cohort study of the German Neonatal Network (GNN). Of the 10,257 VLBW infants, 441 (4.3%) had surgical NEC/FIP. In univariate analyses, the blood group AB was more prevalent in VLBW infants with surgical NEC/FIP compared to non-AB blood groups (OR 1.51, 95% CI 1.07-2.13, p = 0.017; absolute risk difference 2.01%, 95% CI 0.06-3.96%). The association between blood group AB and surgical NEC/FIP was observed in a multivariable logistic regression model (OR of 1.58, 95% CI 1.10-2.26, p = 0.013) as well. In summary, our study suggests that the risk of surgical NEC and FIP is higher in patients with blood group AB and lower in those having non-AB blood groups.

Perirectal intraperitoneal splenosis: A case report of MRI with laparoscopic correlation.

Splenosis is a benign acquired condition, which appears after rupture of the spleen and heterotopic auto-transplantation. Mostly found as an incidental finding on cross-sectional imaging, definitive diagnosis is frequently made histologically after resection or tissue sampling. We report a case of a 36-year-old male patient who presented with increased susceptibility to infections, chronic fatigue, and a history of traumatic splenic rupture. Cross-sectional imaging showed perirectal formations within the mesorectal fascia, and extraperitoneal splenosis was suspected. Due to the radiologically unclear entity of the masses, diagnostic laparoscopy with tissue sampling was performed. Intraoperatively the masses turned out to be intraperitoneal. Histological workup showed splenic tissue, consistent with intraperitoneal splenosis after splenic rupture. In this article we want to discuss important imaging findings and their differentials, as well as clinical implications for this rare entity.

Activity, Plan, and Goal Recognition: A Review.

Recognizing the actions, plans, and goals of a person in an unconstrained environment is a key feature that future robotic systems will need in order to achieve a natural human-machine interaction. Indeed, we humans are constantly understanding and predicting the actions and goals of others, which allows us to interact in intuitive and safe ways. While action and plan recognition are tasks that humans perform naturally and with little effort, they are still an unresolved problem from the point of view of artificial intelligence. The immense variety of possible actions and plans that may be encountered in an unconstrained environment makes current approaches be far from human-like performance. In addition, while very different types of algorithms have been proposed to tackle the problem of activity, plan, and goal (intention) recognition, these tend to focus in only one part of the problem (e.g., action recognition), and techniques that address the problem as a whole have been not so thoroughly explored. This review is meant to provide a general view of the problem of activity, plan, and goal recognition as a whole. It presents a description of the problem, both from the human perspective and from the computational perspective, and proposes a classification of the main types of approaches that have been proposed to address it (logic-based, classical machine learning, deep learning, and brain-inspired), together with a description and comparison of the classes. This general view of the problem can help on the identification of research gaps, and may also provide inspiration for the development of new approaches that address the problem in a unified way.

State of the art treatment for stage I to III anal squamous cell carcinoma: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: This systematic review summarised and critically appraised evidence on the efficacy and safety of interventions for anal cancer to support the panel of experts developing the national evidence-based anal cancer guideline in Germany. MATERIALS AND METHODS: We conducted a systematic review and meta-analyses of interventions for the treatment of stage I to III anal squamous cell carcinoma (SCCA). We systematically searched several databases and included any randomised controlled trial (RCT) assessing the pre-specified patient populations, regardless of the interventions studied. Non-randomised controlled studies of selected, pre-specified interventions were included if RCTs were not available or contained insufficient information. Where possible, we conducted meta-analyses and critically assessed confidence in the effect estimates using the GRADE approach. RESULTS: Our searches yielded 10,325 (25 October 2018) and 889 hits (update search on 18 July 2019). Among the 41 studies (47 publications) included, we identified 19 comparisons of interventions for SCCA, and confidence in the effect estimates ranged from very low to high. Most RCTs compared various chemoradiation regimes. For other treatment options, such as local excision in early stages or different radiotherapies, we mostly identified comparative cohort studies. CONCLUSION: Our findings indicate that, in most clinical situations, primary chemoradiation based on 5-FU and MMC is still the gold standard. However, treatment options for stage I anal cancer, particularly of the anal margin, as well as newer treatment approaches should be investigated in future RCTs. Overall, our findings may help health care professionals and patients make informed decisions about treatment choices.

Fatty acid composition of adipose tissue at term indicates deficiency of arachidonic and docosahexaenoic acid and excessive linoleic acid supply in preterm infants.

BACKGROUND: Arachidonic (ARA) and docosahexaenoic acid (DHA) are constitutive to membrane phospholipids, and essential for brain and overall development. ARA/DHA pools in term infants (TI) are built during the third trimester, stored as adipose tissue triglycerides and predominantly distributed via plasma phosphatidylcholine (PC). In preterm infants (PTI), placental ARA/DHA supply is replaced by linoleic-acid (LA)-enriched nutrition. This study aimed to investigate the impact of PTI nutrition, compared to placental supply, on fatty acid composition in adipose tissue and blood. METHODS: Prospective observational study (4/2017-3/2019) in 12 PTI and 3 PTI with enterostomy (PTI/E) (gestational age (GA) < 32 weeks) with surgical intervention at term (± 6 weeks) and 14 TI (GA ≥ 34 weeks, surgical intervention < 2 weeks postnatally). PTI/E were analyzed descriptively only. PC and triglyceride fatty acids were analyzed with tandem mass spectrometry and gas chromatography, respectively. Results were compared between TI and PTI with Wilcoxon Test and shown as median [25th percentile-75th percentile] mol%. RESULTS: PTI had less ARA in adipose tissue TG (0.77[0.67-0.87]% vs. 1.04[0.95-1.14]%, p = 0.0003) and plasma PC (20.7[18.7-22.8]% vs. 28.3[22.7-33.5]%, p = 0.011) than TI. PTI also had less DHA in adipose tissue TG (0.6[0.4-0.8]% vs. 1.1[0.8-1.4]%, p = 0.006) and plasma PC (6.4[5.6-7.1]% vs. 8.4[7.8-13.1]%, p = 0.002). LA was increased in PTI's adipose tissue TG (10.0[8.8-12.3]% vs. 3.0[2.5-3.6]%, p < 0.0001) and plasma PC (48.4[44.6-49.6]% vs. 30.6[24.9-35.6]%, p = 0.0002). Similar differences were observed in erythrocyte PC. CONCLUSION: In PTI, LA is increased and ARA/DHA decreased in adipose tissue, plasma and erythrocyte lipids as proxies for other tissues, likely caused by PTI nutrition. This may contribute to impaired PTI development.