Preparation of Polyfunctionally Substituted Pyridine-2(1H) thione Derivatives as Precursors to Bicycles and Polycycles

Reaction of acetylacetone with 1 mole of dimethylformamide dimethyl acetal (DMFDMA) affords enamine 2a which react with cyanothioacetamide to give pyridinethione 3a. Pyridinethione 3a reacts with methyl iodide, halogenated compounds, aromatic aldehyde and malononitrile / elemental sulfur to yiled compounds 7-10 respectively. Reactions of thioether (7) in ethanolic K2CO3, 1 mole DMFDMA and 4-(dimethylamino) benzaldehyde gave compounds (11, 13, 14) respectively. Enaminone (12) can be prepared by reaction of compound (11) with DMFDMA. Also, compounds (13) and (14) can be obtained by reaction of compounds (3a) and (9a) with 2 mole of DMFDMA and methyl iodide respectively. Reactions of enaminone (9) with hydrazine hydrate and cyanothioacetamide gave compounds (11) and (12) respectively. Malononitrile dimmer when reacted with chalcones (9a), (14) and enaminone (12), (13) gave bipyridyl (15), (16) and (19a,b) respectively. Bipyridyl (15) can be converted to (16) by methylation using methyl iodide. Reactions of thienopyridine (8) with DMFDMA and sodium nitrite in acetic acid gave tricyclic compounds (20) and (21) respectively. Finally, reactions of (21a) with malononitrile / elemental sulfur and DMFDMA gave compounds (22) and (23) respectively

Preparation of Polyfunctionally Substituted Pyridine-2(1H) thione Derivatives as Precursors to Bicycles and Polycycles

Reaction of acetylacetone with 1 mole of dimethylformamide dimethyl acetal (DMFDMA) affords enamine 2a which react with cyanothioacetamide to give pyridinethione 3a. Pyridinethione 3a reacts with methyl iodide, halogenated compounds, aromatic aldehyde and malononitrile / elemental sulfur to yiled compounds 7-10 respectively. Reactions of thioether (7) in ethanolic K2CO3, 1 mole DMFDMA and 4-(dimethylamino) benzaldehyde gave compounds (11, 13, 14) respectively. Enaminone (12) can be prepared by reaction of compound (11) with DMFDMA. Also, compounds (13) and (14) can be obtained by reaction of compounds (3a) and (9a) with 2 mole of DMFDMA and methyl iodide respectively. Reactions of enaminone (9) with hydrazine hydrate and cyanothioacetamide gave compounds (11) and (12) respectively. Malononitrile dimmer when reacted with chalcones (9a), (14) and enaminone (12), (13) gave bipyridyl (15), (16) and (19a,b) respectively. Bipyridyl (15) can be converted to (16) by methylation using methyl iodide. Reactions of thienopyridine (8) with DMFDMA and sodium nitrite in acetic acid gave tricyclic compounds (20) and (21) respectively. Finally, reactions of (21a) with malononitrile / elemental sulfur and DMFDMA gave compounds (22) and (23)respectively.Keywords: Acetyl acetone; DMFDMA; Malononitrile dimmer; Bipyridyl; 5-Acetylpyridinethione

Seroprevalence of Toxoplasma gondii infection in arthritis patients in eastern China

Background: There is accumulating evidence for an increased susceptibility to infection in patients with arthritis. We sought to understand the epidemiology of Toxoplasma gondii infection in arthritis patients in eastern China, given the paucity of data on the magnitude of T. gondii infection in these patients. Methods: Seroprevalence of T. gondii infection was assessed by enzyme-linked immunosorbent assay using a crude antigen of the parasite in 820 arthritic patients, and an equal number of healthy controls, from Qingdao and Weihai cities, eastern China. Sociodemographic, clinical and lifestyle information on the study participants were also obtained. Results: The prevalence of anti-T. gondii IgG was significantly higher in arthritic patients (18.8%) compared with 12% in healthy controls (P < 0.001). Twelve patients with arthritis had anti-T. gondii IgM antibodies comparable with 10 control patients (1.5% vs 1.2%). Demographic factors did not significantly influence these seroprevalence frequencies. The highest T. gondii infection seropositivity rate was detected in patients with rheumatoid arthritis (24.8%), followed by reactive arthritis (23.8%), osteoarthritis (19%), infectious arthritis (18.4%) and gouty arthritis (14.8%). Seroprevalence rates of rheumatoid arthritis and reactive arthritis were significantly higher when compared with controls (P < 0.001 and P = 0.002, respectively). A significant association was detected between T. gondii infection and cats being present in the home in arthritic patients (odds ratio [OR], 1.68; 95% confidence interval [CI]: 1.24 – 2.28; P = 0.001). Conclusions: These findings are consistent with and extend previous results, providing further evidence to support a link between contact with cats and an increased risk of T. gondii infection. Our study is also the first to confirm an association between T. gondii infection and arthritis patients in China. Implications for better prevention and control of T. gondii infection in arthritis patients are discussed. Trial registration: This is an epidemiological survey, therefore trial registration was not required

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Search for Resonant Production of High-Mass Photon Pairs in Proton-Proton Collisions at root s=8 and 13 TeV

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