2-(Morpholin-4-yl)-6-(1H-pyrrol-1-yl)­pyridine-3,5-dicarbonitrile

In the title compound, C15H13N5O, the morpholine ring adopts a chair conformation. The dihedral angle between the pyrrole ring and the pyridine ring is 28.93 (14)°. In the crystal, the molecules are linked by C—H⋯O hydrogen bonds occur, and aromatic weak π–π stacking [centroid–centroid separation = 4.178 (2) Å] and C—H⋯π inter­actions consolidate the packing

2-Amino-6-(dimethyl­amino)pyridine-3,5-dicarbonitrile

The title compound, C9H9N5, is slightly twisted from planarity, with a maximum deviation of 0.0285 (13) Å from the pyridine plane for the C atom bearing the amino group. The cyano groups are on different sides of the pyridine plane, with C- and N-atom deviations of 0.072 (3)/0.124 (4) and −0.228 (4)/−0.409 (5) Å from the pyridine plane. In the crystal, N—H⋯N and C—H⋯N hydrogen bonds connect the mol­ecules into zigzag chains running along the c axis

2-(Piperidin-1-yl)-6-(1H-pyrrol-1-yl)pyridine-3,5-dicarbonitrile

The piperidine ring of the title compound, C16H15N5, adopts a chair conformation. The pyridine ring is essentially planar, with a maximum deviation of 0.035 (3) Å. The pyrrole and pyridine rings are almost coplanar, forming a dihedral angle of 3.48 (14)°. In the crystal, no classical hydrogen bonds were found. In the crystal, the molecules are linked by aromatic π–π stacking [centroid–centroid separations = 3.4984 (16) and 3.9641 (15) Å between pyrrole and pyridine rings and between pyridine rings, respectively]

Can Bcl-XL expression predict the radio sensitivity of Bilharzial-related squamous bladder carcinoma? a prospective comparative study

<p>Abstract</p> <p>Background</p> <p>Local pelvic recurrence after radical cystectomy for muscle invasive bilharzial related squamous cell carcinoma accounts for 75% of treatment failures even in organ confined tumors. Despite the proven value of lymphadenectomy, up to 60% of patients undergoing cystectomy do not have it. These factors are in favor of adjuvant radiotherapy reevaluation. objectives: to evaluate the effect of adjuvant radiotherapy on disease free survival in muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder and to test the predictability of radio-sensitivity using the anti apoptotic protein Bcl-XL.</p> <p>Methods</p> <p>The study prospectively included 71 patients, (47 males, 24 females) with muscle invasive bilharzial related squamous cell carcinoma of the bladder (Stage pT2a-T3N0-N3M0) who underwent radical cystectomy in Assiut university hospitals between January 2005 and December 2006. Thirty eight patients received adjuvant radiotherapy to the pelvis in the dose of 50Gy/25 fractions/5 weeks (Group 1), while 33 patients did not receive adjuvant radiotherapy (group 2). Immunohistochemical characterization for bcl-xL expression was done. Follow up was done every 3 months for 12 to 36 months with a mean of 16 ± 10 months. All data were analyzed using SPSS version 16. Three years cumulative disease free survival was calculated and adjusted to Bcl-XL expression and side effects of the treatment were recorded.</p> <p>Results</p> <p>The disease free cumulative survival was 48% for group 1 and 29% for group 2 (log rank p value 0.03). The multivariate predictors of tumor recurrence were the positive Bcl-XL expression (odd ratio 41.1, 95% CI 8.4 - 102.3, p < 0.0001) and radiotherapy (odd ratio 0.19, 95% CI 0.05 - 0.78, p < 0.02). With Cox regression, the only independent multivariate predictor of radio-sensitivity was the Bcl-XL expression with odd ratio 4.6 and a p value < 0.0001. All patients tolerated the treatment with no life threatening or late complications during the period of follow up.</p> <p>Conclusions</p> <p>Adjuvant radiotherapy for muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder has potential effectiveness and minor side effects. Moreover, Bcl-XL expression is a valuable tool for predicting those who might not respond to this adjuvant treatment.</p

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

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

2,2&#8242;-[Ethane-1,2-diylbis(oxy)]dibenzaldehyde

In the title compound, C16H14O4, the benzene rings are inclined at a dihedral angle of 75.14&#8197;(9)&#176;. The torsion angle of the bridging O&#8212;C&#8212;C&#8212;O group is &#8722;76.50&#8197;(11)&#176;. In the crystal, molecules are linked by C&#8212;H...O hydrogen bonds, forming C(6) chains along [100]. Furthermore, C&#8212;H...&#960; interactions and &#960;&#8211;&#960; stacking interactions [centroid&#8211;centroid distances = 3.6957&#8197;(7) and 3.6735&#8197;(8)&#8197;&#197;] contribute to the stability of the crystal packing

1-((E)-{2-[4-(2-{(1E)-[(carbamothioylamino)imino]methyl}phenoxy)butoxy]benzylidene}amino)thiourea dimethyl sulfoxide disolvate

The title compound, C20H24N6O2S2·2C2H6OS, has crystallographically imposed centrosymmetry. The packing is assisted by N—H...O, C—H...O and N—H...S interactions with the lattice solvent molecules, forming a two-dimensional network parallel to (1-10). The lattice dimethyl sulfoxide molecules (except for the S atoms) were modelled over two sites with refined occupancies of 0.831 (3):0.169 (3)

The interplay of solvation, molecular conformation and supramolecular assembly in 1,1'-({[(ethane-1,2-diyl) dioxy](1,2-phenylene)} bis(methanylylidene))bis(thiosemicarbazide) and its N, N-dimethylformamide disolvate

The wide diversity of applications of thiosemicarbazones and bis(thiosemicarbazones) has seen them used as anticancer and antitubercular agents, and as ligands in metal complexes designed to act as site-specific radiopharmaceuticals. Molecules of 1,10-({[(ethane-1,2-diyl) dioxy](1,2-phenylene)} bis(methanylylidene))bis(thiosemicarbazide) {alternative name: 2,20-[ethane-1,2-diylbis(oxy)] dibenzaldehyde bis(thiosemicarbazide)}, C18H2ON6O2S2, (I), lie across twofold rotation axes in the space group C2/c, with an O-C-C-O torsion angle of -59.62 (13)degrees and a trans-planar arrangement of the thiosemicarbazide fragments relative to the adjacent aryl rings. The molecules of (I) are linked by N-H center dot center dot center dot S hydrogen bonds to form sheets containing R-4(2)(38) rings and two types of R 2 2(8) ring. In the N, N-dimethylformamide disolvate, C18H2ON6O2S2 -2C(3)H(7)NO, (II), the independent molecular components all lie in general positions, but one of the solvent molecules is disordered over two sets of atomic sites having occupancies of 0.839 (3) and 0.161 (3). The O-C-C-O torsion angle in the ArOCH2CH2OAr component is -75.91 (14)degrees and the independent thiosemicarbazide fragments both adopt a cis-planar arrangement relative to the adjacent aryl rings. The ArOCH2CH2OAr components in (II) are linked by N-H center dot center dot center dot S hydrogen bonds to form deeply puckered sheets containing R-2(2)(8), R-4(2)(8) and two types of R-2(2)(38) rings, and which contain cavities which accommodate all of the solvent molecules in the interior of the sheets. Comparisons are made with some related compounds

Triclinic and monoclinic polymorphs of meso-(E,E)1,1 '-[1,2-bis(4-chlorophenyl)ethane-1,2-diyl]bis(phenyldiazene): the high-yield synthesis of an unexpected product, concomitant polymorphism and configurational disorder

Pyrazolidine-3,5-diones and their derivatives exhibit a wide range of biological activities. Seeking to explore the effect of combining a hydrocarbyl ring substituent, as present in sulfinpyrazone (used to treat gout), with a chlorinated aryl ring, as present in muzolimine (a diuretic), we explored the reaction between 1-phenylpyrazolidine-3,5-dione and 4-chlorobenzaldehyde under mildly basic conditions in the expectation of producing the simple condensation product 4-(4-chlorobenzylidene)-1-phenylpyrazolidine-3,5-dione. However, the reaction product proved to be meso-(E,E)-1,1'-[1,2-bis(4-chlorophenyl)ethane-1,2-diyl]bis(phenyldiazene), C26H20Cl2N4, and a tentative mechanism is proposed. Crystallization from ethanol produces two concomitant polymorphs, i.e. a triclinic form, (I), in the space group P (1) over bar, and a monoclinic form, (II), in the space group C2/c. In both polymorphs, the molecules lie across centres of inversion, but in (II), the molecules are subject to whole-molecule disorder equivalent to configurational disorder with occupancies of 0.6021 (19) and 0.3979 (19). There are no hydrogen bonds in the crystal structure of polymorph (I), but the molecules of polymorph (II) are linked by C-H center dot center dot center dot pi (arene) hydrogen bonds into complex chains, which are further linked into sheets by C-H center dot center dot center dot N interactions