Oxidative cyclisation and methylene insertion in 1,3-indandione derivatives .The mechanistic studies

Dimethyl sulphoxide activated by acetic-anhydride introduces methylthiomethyl group into phenols,oxidises certain medicinally useful secondary alcohols to their corresponding ketones and brings about oxidative rearrangements in different substrates.It converts 4-hydroxy coumarins and dicoumarols,under varying conditions,to a variety of products of both pharmaceutical and mechanistic interest. When1,3-indandione (1) was interacted with this versatile reagent at water bath temperature,it  afforded an ylide (2) and an oxidative cyclisation product (3).However,its interaction with Ar –CH = (CN)R,leads to the formation of a mechanistically interesting compound,indeno[1,2-b]-4H pyran(4).   DMSO alone has been used as a reagent and yields a number of products of mechanistic interest with different substrates.When 1,3-indandione (1) was refluxed with DMSO alone at elevated temperature,it results the formation of poly(methylene-bis) 1,3-indandione(5) involving methylene group insertion between different 1,3-indandione moieties.Methylene insertion has also been observed when 1,3-indandione (1) was condensed with formaldehyde in presence of alkali carbonates or primary amines to yield (6)and(7) respectively

Synthesis of Unusual Trimers in 1,3-Indandione

Dimethyl Sulphoxide-acetic anhydride reagent converts 1,3-indandione to the ylide (2) and a much awaited dimer (3) at room temperature. However , when 1,3-indandione was interacted with pre- heated  DMSO-acetic anhydride  at  waterbath temperature it affords an unusual trimer (4) and a novel compound (5), methine-tris-1,3-indandione  along with the ylide (2) Key words: DMSO, Acetic anhydride, Indandione,Ylide Trimer

Disorder and excess modes in hard-sphere colloidal systems

The anomalous thermodynamic properties of glasses remain incompletely understood, notably the anomalous peak in the heat capacity at low temperatures; it is believed to be due to an excess of low-frequency vibrational modes and a manifestation of the structural disorder in these systems. We study the thermodynamics and vibrational dynamics of colloidal glasses and (defected) crystals. The experimental determination of the vibrational density of states allows us to directly observe a strong enhancement of low-frequency modes. Using a novel method (Zargar R. et al., Phys. Rev. Lett. 110 (2013) 258301) to determine the free energy, we also determine the entropy and the specific heat experimentally. It follows that the emergence of the excess modes and high values of the specific heat are directly related and are specific to the glass: even for solids containing a very large amount of defects, both the low-frequency density of states and the specific heat are significantly smaller than for the glass

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy

© Springer-Verlag GmbH Germany, part of Springer Nature 2018Background: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. Patients and methods: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. Results: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the ‘CIS’ versus ‘no-CIS’ groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63–1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01–1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23–2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34–0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82–1.35; p = 0.70). Conclusion: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.Peer reviewedFinal Accepted Versio

Post-Partum Pituitary Insufficiency and Livedo Reticularis Presenting a Diagnostic Challenge in a Resource Limited Setting in Tanzania: A Case Report, Clinical Discussion and Brief Review of Existing Literature.

Pituitary disorders following pregnancy are an important yet under reported clinical entity in the developing world. Conversely, post partum panhypopituitarism has a more devastating impact on women in such settings due to high fertility rates, poor obstetric care and scarcity of diagnostic and therapeutic resources available. A 37 year old African female presented ten years post partum with features of multiple endocrine deficiencies including hypothyroidism, hypoadrenalism, lactation failure and secondary amenorrhea. In addition she had clinical features of an underlying autoimmune condition. These included a history of post-partum thyroiditis, alopecia areata, livedo reticularis and deranged coagulation indices. A remarkable clinical response followed appropriate hormone replacement therapy including steroids. This constellation has never been reported before; we therefore present an interesting clinical discussion including a brief review of existing literature. Post partum pituitary insufficiency is an under-reported condition of immense clinical importance especially in the developing world. A high clinical index of suspicion is vital to ensure an early and correct diagnosis which will have a direct bearing on management and patient outcome

The burden of diabetes mellitus during pregnancy in low- and middle-income countries : a systematic review

Peer reviewedPublisher PD

Management of Portal Hypertension in Children

Management of portal hypertension in children has evolved over the past several decades. Portal hypertension can result from intrahepatic or extrahepatic causes. Management should be tailored to the child based on the etiology of the portal hypertension and on the functionality of the liver. The most serious complication of portal hypertension is gastroesophageal variceal bleeding, which has a mortality of up to 30%. Initial treatment of bleeding focuses on stabilizing the patient. Further treatment measures may include endoscopic, medical, or surgical interventions as appropriate for the child, depending on the cause of the portal hypertension. β-Blockers have not been proven to effectively prevent primary or secondary variceal bleeding in children. Sclerotherapy and variceal band ligation can be used to stop active bleeding and can prevent bleeding from occurring. Transjugular intrahepatic portosystemic shunts and surgical shunts may be reserved for those who are not candidates for transplant or have refractory bleeding despite medical or endoscopic treatment

Barriers and facilitators to provide effective pre-hospital trauma care for road traffic injury victims in Iran: a grounded theory approach

BACKGROUND: Road traffic injuries are a major global public health problem. Improvements in pre-hospital trauma care can help minimize mortality and morbidity from road traffic injuries (RTIs) worldwide, particularly in low- and middle-income countries (LMICs) with a high rate of RTIs such as Iran. The current study aimed to explore pre-hospital trauma care process for RTI victims in Iran and to identify potential areas for improvements based on the experience and perception of pre-hospital trauma care professionals. METHODS: A qualitative study design using a grounded theory approach was selected. The data, collected via in-depth interviews with 15 pre-hospital trauma care professionals, were analyzed using the constant comparative method. RESULTS: Seven categories emerged to describe the factors that hinder or facilitate an effective pre-hospital trauma care process: (1) administration and organization, (2) staff qualifications and competences, (3) availability and distribution of resources, (4) communication and transportation, (5) involved organizations, (6) laypeople and (7) infrastructure. The core category that emerged from the other categories was defined as "interaction and common understanding". Moreover, a conceptual model was developed based on the categories. CONCLUSIONS: Improving the interaction within the current pre-hospital trauma care system and building a common understanding of the role of the Emergency Medical Services (EMS) emerged as key issues in the development of an effective pre-hospital trauma care process

The requirements and challenges in preventing of road traffic injury in Iran. A qualitative study

<p>Abstract</p> <p>Background</p> <p>Road traffic injuries (RTIs) are a major public health problem, especially in low- and middle-income countries. Among middle-income countries, Iran has one of the highest mortality rates from RTIs. Action is critical to combat this major public health problem. Stakeholders involved in RTI control are of key importance and their perceptions of barriers and facilitators are a vital source of knowledge. The aim of this study was to explore barriers to the prevention of RTIs and provide appropriate suggestions for prevention, based on the perceptions of stakeholders, victims and road-users as regards RTIs.</p> <p>Methods</p> <p>Thirty-eight semi-structured interviews were conducted with informants in the field of RTI prevention including: police officers; public health professionals; experts from the road administrators; representatives from the General Governor, the car industry, firefighters; experts from Emergency Medical Service and the Red Crescent; and some motorcyclists and car drivers as well as victims of RTIs. A qualitative approach using grounded theory method was employed to analyze the material gathered.</p> <p>Results</p> <p>The core variable was identified as "The lack of a system approach to road-user safety". The following barriers in relation to RTI prevention were identified as: human factors; transportation system; and organizational coordination. Suggestions for improvement included education (for the general public and targeted group training), more effective legislation, more rigorous law enforcement, improved engineering in road infrastructure, and an integrated organization to supervise and coordinate preventive activities.</p> <p>Conclusion</p> <p>The major barriers identified in this study were human factors and efforts to change human behaviour were suggested by means of public education campaigns and stricter law enforcement. However, the lack of a system approach to RTI prevention was also an important concern. There is an urgent need for both an integrated system to coordinate RTI activities and prevention and a major change in stakeholders' attitudes towards RTI prevention. The focus of all activities should take place on road users' safety.</p

Investigating the Responses of Human Epithelial Cells to Predatory Bacteria

One beguiling alternative to antibiotics for treating multi-drug resistant infections are Bdellovibrio-and-like-organisms (BALOs), predatory bacteria known to attack human pathogens. Consequently, in this study, the responses from four cell lines (three human and one mouse) were characterized during an exposure to different predatory bacteria, Bdellovibrio bacteriovorus HD100, Bacteriovorus BY1 and Bacteriovorax stolpii EB1. TNF-alpha levels were induced in Raw 264.7 mouse macrophage cultures with each predator, but paled in comparison to those obtained with E. coli. This was true even though the latter strain was added at an 11.1-fold lower concentration (p &lt; 0.01). Likewise, E. coli led to a significant (54%) loss in the Raw 264.7 murine macrophage viability while the predatory strains had no impact. Tests with various epithelial cells, including NuLi-1 airway, Caco2, HT29 and T84 colorectal cells, gave similar results, with E. coli inducing IL-8 production. The viabilities of the NuLi-1 and Caco-2 cells were slightly reduced (8%) when exposed to the predators, while T84 viability remained steady. In no cases did the predatory bacteria induce actin rearrangement. These results clearly demonstrate the gentle natures of predatory bacteria and their impacts on human cells.ope