Efficient synthesis of novel bis(dihydropyrano[2,3c]pyrazoles), bis(4H-chromenes) and bis(dihydropyrano[3,2-c]chromenes) with amide functionality

A synthesis of novel bis(1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles), bis(4H-chromene-3-carbonitriles) and bis(dihydropyrano[3,2-c]chromenes), which are linked to aliphatic spacers via amide linkages was achieved via multicomponent reactions (MCR) of the appropriate bis-aldehyde with two equivalents of both of malononitrile and 3-methylpyrazol-5-one, dimedone or 4-hydroxycoumarin in a basic solution

Biostratigraphy and Paleoenvironmental Reconstruction at the Gebel Nezzazat (Central Sinai, Egypt): A Paleocene Record for the Southern Tethys

The variations in assemblages of calcareous nannofossils are tracked in the Dakhla and Tarawan Formations exposed at Gebel Nezzazat (central Sinai, Egypt). Five calcareous nannofossil biozones, namely NP2/3, NP4, NP5, NP6, and NP7/8 are identified. A distinct marker bed related to the Latest Danian Event (LDE) occurs within the Dakhla Fm. The earliest representative of fasciculiths, Lithoptychius schmitzii, first occurs just below the LDE distinct bed and is followed by the Los of Diantholitha alata, D. mariposa, L. varolii, L. felis, and L. collaris. The abundance of calcareous nannofossils drops within the LDE distinctive bed. The base of Selandian Stage is here approximated at the base of Zone NP5 in concurrence with a sudden drop in the abundance of calcareous nannofossils. No considerable lithological changes are noted across this transition. The absence of subsequent occurrences of L. ulii, L. janii, L. billii, and L. stegostus suggest inconsistent lowest occurrences (Los) of these taxa, insufficient sampling resolution, and/or a hiatus. The base of Thanetian is approximated with the base of Zone NP7/8 in the topmost of Dakhla Fm. No considerable changes in calcareous nannofossil assemblages are associated in correspondence to this transition except the LO of D. mohleri, lowest continuous occurrence (LctO) of Bomolithus megastypus, and the increase in abundance of Heliolithus kleinpellii as well as a sudden drop in abundance within Zone NP7/8. The variations in calcareous nannofossil assemblages at Gebel Nezzazat suggest prevailing warm-water and oligotrophic conditions during the Paleocene and particularly along the Danian Stage that are interrupted by minor fluctuations in paleoclimatic conditions. In particular, the Danian–Selandian transition marks a decrease in warm and oligotrophic conditions that persisted along the Selandian Stage. The Selandian–Thanetian transition shows an increase of warm and oligotrophic conditions prevailed in the Thanetian record. The sudden decrease in abundance of calcareous nannofossils in both the Selandian and Thanetian is likely resulted from an increase in dissolution of carbonates rather than variations in the paleotemperature and/or paleofertility

New Azacycles by One-Pot Three-Component Hantzsch-Like Synthesis of Tetra(hexa)azacyclopenta[a]anthracenes, Tetraazaindeno[5,4-b]fluorenes, and Oxatetraazacyclopenta[m]tetraphenes

Multicomponent reactions (MCRs) are envisaged as an entry point for the synthesis of heterocyclic compounds with interesting biological activities. An efficient approach to annelated tetra(hexa)azacyclopenta[a]anthracenes, tetraazaindeno[5,4-b]fluorenes, and oxatetraazacyclopenta[m]tetraphene was accomplished using a three-component reaction involving 7-amino-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-5-one with aromatic aldehydes and the corresponding active 1,3-dicarbonyl compounds (namely, dimedone, 1,3-dimethylbarbituric acid, 1,3-indanedione, and 4-hydroxycoumarine). The reactions were conducted in glacial acetic acid at reflux for 5 h to give the desired products in good yields (62–83 %). The chemical constitutions of all new products were confirmed spectroscopically

Magnetic resonance imaging of head and neck vascular anomalies: pearls and pitfalls

Purpose: The aim of this study was to describe typical MRI features of the head and neck vascular anomalies and the possible diagnostic pitfalls.Patients and methods: Patients with extracranial vascular anomalies of the head and neck, who underwent MRI examinations between January 2013 and January 2016, were included in the study. Precontrast and postcontrast T1-WI,T2-WI, with and without fat saturation were acquired. When indicated, a noncontrast MR angiography was performed. Dynamic postcontrast MRI techniques were available in six children.Results: The study included 33 patients (age ranged from 10 to 20 years, mean: 49 months). MRI confirmed the clinical diagnosis in equivocal cases, and provided proper determination of lesion extension and/or associated intracranial anomalies. The study included 10 cases of vascular tumors (hemangioma), whereas the remaining 23 cases had the diagnosis of vascular malformations (one patient with arteriovenous malformation, one with capillary malformation, seven with venous, nine with macrocystic lymphatic, and five with microcystic lymphatic malformations).Conclusion: Vascular anomalies in the head and neck are mostly diagnosed on clinical basis; however, when the history is uncertain or the diagnosis is equivocal, a well-tailored MR examination can be a single valuable diagnostic tool providing structural and functional information.Keywords: children, head and neck, hemangioma, lymphatic malformation, magnetic resonance angiography, venous malformatio

Feasibility of a Novel Sparse Orthogonal Collimator–Based Preclinical Total Marrow Irradiation for Enhanced Dosimetric Conformality

Total marrow irradiation (TMI) has significantly improved radiation conditioning for hematopoietic cell transplantation in hematologic diseases by reducing conditioning-induced toxicities and improving survival outcomes in relapsed/refractory patients. Recently, preclinical three-dimensional image–guided TMI has been developed to enhance mechanistic understanding of the role of TMI and to support the development of experimental therapeutics. However, a dosimetric comparison between preclinical and clinical TMI reveals that the preclinical TMI treatment lacks the ability to reduce the dose to some of the vital organs that are very close to the skeletal system and thus limits the ability to evaluate radiobiological relevance. To overcome this limit, we introduce a novel Sparse Orthogonal Collimator (SOC)–based TMI and evaluate its ability to enhance dosimetric conformality. The SOC-TMI–based dose modulation technique significantly improves TMI treatment planning by reducing radiation exposures to critical organs that are close to the skeletal system that leads to reducing the gap between clinical and preclinical TMI

Role of Inflammatory Cytokines in Obese and Nonobese Diabetic Children

BACKGROUND: Obesity is an expanded health problem worldwide and it is blamed for a startling rise in type 1 diabetes (T1DM), the interaction between obesity, autoimmune processes, and glucose homeostasis is a growing field of study. AIM: This study was undertaken to predict the role of the inflammatory cytokines (interleukin [IL]-17 and IL-10) as biomarkers in early screening for obesity and T1DM and to determine the relation of inflammatory cytokines with diabetic complications especially nephropathy. SUBJECTS AND METHODS: The target group consisted of 92 children with type 1 diabetes children who were diagnosed according to the criteria provided by American Diabetes Association Diabetic; cases were divided into two groups, Group 1 (overweight and obese diabetics) and Group 2 (normal weight diabetic children). The levels of serum IL-17 and IL-10 were assayed in these children by an enzyme-linked immunosorbent assay. Serum triglycerides (TG) and cholesterol levels were measured as well as urinary microalbumin level was estimated for detection of nephropathy. RESULTS: Diabetic overweight and obese children exhibited significantly 3.8 folds more at risk to be bad glycemic control than diabetic children with normal body mass index (BMI). Furthermore, overweight and obese diabetic children displayed significantly 15 times more at risk of having nephropathy than diabetic children with normal BMI. Low serum level of IL 10 and high level of IL 17 showed a significant association with high BMI in diabetic children. High HBA1c, low IL 10, and long disease duration were significantly considered as predominant risk factors for diabetic nephropathy in diabetic children. CONCLUSION: The obtained data from these investigations proved that overweight and obese children have a low serum level of IL-10 and high serum IL-17 levels. The relationship between IL-10/IL-17 can be applied as a good marker for the inflammatory state and these inflammatory interleukins can be employed as biomarkers in early screening for obesity and T1DM. Furthermore, these interleukins can be utilized as a predictor for early diabetic complications, particularly nephropathy

A prospective multicentre study evaluating the outcomes of the abdominal wall dehiscence repair using posterior component separation with transversus abdominis muscle release reinforced by a retro-muscular mesh: filling a step

Background This study aimed to evaluate the results of posterior component separation (CS) and transversus abdominis muscle release (TAR) with retro-muscular mesh reinforcement in patients with primary abdominal wall dehiscence (AWD). The secondary aims were to detect the incidence of postoperative surgical site occurrence and risk factors of incisional hernia (IH) development following AWD repair with posterior CS with TAR reinforced by retromuscular mesh. Methods Between June 2014 and April 2018, 202 patients with grade IA primary AWD (Björck’s first classification) following midline laparotomies were treated using posterior CS with TAR release reinforced by a retro-muscular mesh in a prospective multicenter cohort study. Results The mean age was 42 ± 10 years, with female predominance (59.9%). The mean time from index surgery (midline laparotomy) to primary AWD was 7 ± 3 days. The mean vertical length of primary AWD was 16 ± 2 cm. The median time from primary AWD occurrence to posterior CS + TAR surgery was 3 ± 1 days. The mean operative time of posterior CS + TAR was 95 ± 12 min. No recurrent AWD occurred. Surgical site infections (SSI), seroma, hematoma, IH, and infected mesh occurred in 7.9%, 12.4%, 2%, 8.9%, and 3%, respectively. Mortality was reported in 2.5%. Old age, male gender, smoking, albumin level < 3.5 gm%, time from AWD to posterior CS + TAR surgery, SSI, ileus, and infected mesh were significantly higher in IH. IH rate was 0.5% and 8.9% at two and three years, respectively. In multivariate logistic regression analyses, the predictors of IH were time from AWD till posterior CS + TAR surgical intervention, ileus, SSI, and infected mesh. Conclusion Posterior CS with TAR reinforced by retro-muscular mesh insertion resulted in no AWD recurrence, low IH rates, and low mortality of 2.5%. Trial registration Clinical trial: NCT05278117

Effect of Physical Exercise on Bone Density and Remodeling in Egyptian Type 1 Diabetic Osteopenic Adolescents

<p>Abstract</p> <p>Background</p> <p>The study was planned to assess effect of physical exercise on bone remodeling in type I diabetics with osteopenia.</p> <p>Methods</p> <p>Twenty-four type I diabetes mellitus (DM1) with osteopenia (10 females and 14 males) were compared to thirty-eight age- and sex-matched healthy control individuals (20 females and 18 males) for biochemical and radiologic parameters of bone mass. Laboratory investigations included serum and urinary calcium, inorganic phosphorus, alkaline phosphatase, and serum "procollagen type 1 N-terminal propeptide (P1NP). Bone densitometry was assessed at neck femur using Dual Energy X-ray Absorptiometry (DEXA). Serum P1NP and DEXA were reevaluated after a planned exercise program.</p> <p>Results</p> <p>Patients and controls were comparable with respect to serum as well as urinary biochemical parameters of bone mass namely; calcium, phosphorus and total serum alkaline phosphatase. Osteopenic DM1 patients displayed lower mean serum P1NP than control group (20.11 ± 6.72 ugdL versus 64.96 ± 34.89 ugdL; p < 0.05). A significant correlation was observed between BMD and degree of glycemic control reflected by serum glycated hemoglobin (r = -0.44, p, 0.030). Bone densitometry correlated with serum P1NP (r = -0.508, p, 0.011). After a planned regular exercise for 3 months, serum P1NP and BMD levels increased with percentage change of 40.88 ± 31.73 and 3.36 ± 2.94, respectively. Five patients resumed normal densitometry and they were all males.</p> <p>Conclusion</p> <p>Diabetic osteopenic patients displayed lower serum levels of procollagen type 1 N-terminal propeptide which reflects poor bone formation. A 3-months planned exercise program was associated with improvement of bone densitometry and significant increment of serum P1NP.</p

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020