Design, synthesis and evaluation of small molecules as inhibitors of plasminogen activator inhibitor-1

Plasminogen activator inhibitor type-1 (PAI-1) is a member of the serine protease inhibitor (serpin) superfamily. Excessive levels of PAI-1 inhibit urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), which regulates fibrinolysis as well as the development of different pathological diseases like obesity, metabolic syndrome, tumor invasion and metastasis, and coronary heart disease. Currently, there is no Food and Drug Administration approval for inactivating higher levels of PAI-1. Therefore, PAI-1 is considered an attractive drug target. Due to PAI-1’s different structural conformations and multiple binding domains, development of PAI-1 inhibitors is a challenging situation. In this research study, we describe the synthesis and evaluation of novel low molecular weight amides containing various moieties, including para-chlorobenzyl, polyphenol, oxindole, or isatin-based units. By changing the architectural scheme of these compounds we hope to effectively change the potency of our inhibitors, and will be able to develop a structure-activity relationship that will allow us to design a more potent small molecule as a PAI-1 inhibitor. Therefore, the synthesis and structure-activity relationship of those novel small molecules are discussed in this paper

Language-Mixing in Discourse in Bilingual Individuals with Non-Fluent Aphasia

Language-mixing (LM) as defined by Chengappa (2009, p. 417) is an “intra-sentential phenomenon referred to as the mixing of various linguistic units (morphemes, words, modifiers, phrases, etc.), primarily from two participating grammatical systems”. LM is influenced by grammatical, environmental, and social constraints (e.g., Milroy & Wei, 1995; Bhat & Chengappa, 2005). Researchers have suggested that LM in patients with aphasia is a communicative strategy used to achieve successful exchanges between speakers; the effectiveness of this mixing, however, had yet to be demonstrated quantitatively. In the current study we investigated whether LM is present in bilingual speakers with aphasia, and if so, at which linguistic level(s) (morphological, lexical, pragmatic, and phrase) LM is found. Once these questions were addressed, we asked whether the LM patterns were typical or atypical in nature in such individuals. Finally, we investigated the differences in pertinent discourse measures (productivity, dysfluencies, coherence, and communicative success) in bilingual speakers with and without aphasia in order to assess if LM truly helps them to produce a more successful form of communication. A total of 64 individuals – one group of 32 bilingual individuals with non-fluent aphasia and another group of 32 bilingual healthy control participants were recruited from local hospitals in Mysore, India. The study made use of two types of discourse elicitation tasks: personal narratives and picture description. Healthy control and aphasia participant groups were encouraged to mix languages in one condition. Their performance in this condition was compared to when they were constrained from mixing in Kannada-only and English-only conditions. Investigating brain damaged and non-brain damaged bilingual speakers from the same speech community allowed for the interpretation of typical and atypical patterns of language usage. The LM patterns that were similar in both groups, hence typical in nature were direction of LM, LM at various levels, LM frequency across tasks, and LM in different word classes. We observed four atypical patterns of language-mixing in individuals with aphasia: 1) they produced a higher percentage of mixing compared to the healthy control participants; 2) they produced a higher percentage of mixing in the Kannada-only condition than the English-only condition, i.e., they did not follow the instructions provided by the examiner during the Kannada-only condition; 3) they produced Kannada matrix language utterances in the English-only condition, which is atypical in the local Kannada-English speaking community; and 4) they produced more word-level mixing during Kannada-only and language-mixed condition than the English-only condition. It is common practice for clinicians and researchers to promote the usage of two or more languages, as they believe it enhances communication (e.g., Muñoz et al., 1999; Chengappa, et al., 2004). However, in the current study, we found that the ability to use more than one language did not lead to a more successful form of communication. We found that individuals with aphasia produced more morphemes, words, phrases, and utterances when they mixed languages, but they did not score higher on the communicative success and coherence scales compared to when they were constrained from mixing

Successful non-surgical management of acute, uncomplicated appendicitis in pregnancy: A case report

Acute appendicitis during pregnancy is one of the most common non-obstetric indications for surgery during pregnancy. Prompt surgical intervention for appendicitis is considered the standard of care. However, data on the utility of surgical management of uncomplicated cases of appendicitis is inconclusive and effectiveness of non-surgical management is currently understudied. We present a case that provides evidence for successful, antibiotic management of uncomplicated appendicitis as a means to reduce the burden of surgical complications on the pregnant population. This article also offers a critical analysis of current standard of care and assesses feasibility of nonsurgical management of acute, uncomplicated appendicitis in pregnancy for well-selected patients

Comparative Study of RSS-Based Collaborative Localization Methods in Wireless Sensor Networks

In this thesis two collaborative localization techniques are studied: multidimensional scaling (MDS) and maximum likelihood estimator (MLE). A synthesis of a new location estimation method through a serial integration of these two techniques, such that an estimate is first obtained using MDS and then MLE is employed to fine-tune the MDS solution, was the subject of this research using various simulation and experimental studies. In the simulations, important issues including the effects of sensor node density, reference node density and different deployment strategies of reference nodes were addressed. In the experimental study, the path loss model of indoor environments is developed by determining the environment-specific parameters from the experimental measurement data. Then, the empirical path loss model is employed in the analysis and simulation study of the performance of collaborative localization techniques

Sustainable enzymatic treatment of organic waste in a framework of circular economy

Enzymatic treatment of food and vegetable waste (FVW) is an eco-friendly approach for producing industrially relevant value-added products. This review describes the sources, activities and potential applications of crucial enzymes in FVW valorization. The specific roles of amylase, cellulase, xylanase, ligninase, protease, pectinase, tannase, lipase and zymase enzymes were explained. The exhaustive list of value-added products that could be produced from FVW is presented. FVW valorization through enzymatic and whole-cell enzymatic valorization was compared. The note on global firms specialized in enzyme production reiterates the economic importance of enzymatic treatment. This review provides information on choosing an efficient enzymatic FVW treatment strategy, such as nanoenzyme and cross-linked based enzyme immobilization, to make the process viable, sustainable and cheaper. Finally, the importance of life cycle assessment of enzymatic valorization of FVW was impressed to prove this approach is a better option to shift from a linear to a circular economy

Obstetric care among refugee populations: reinforcing cultural humility in residency training—preliminary report

The burden of increasing obstetric morbidity and mortality in the United States disproportionately impacts certain populations more than others, one such group being refugees. Poor obstetric outcomes among refugee communities historically have been attributed to delayed initiation of prenatal care, failure to detect co-morbidities, as well as higher rates of Cesarean sections (C-sections), stillbirths, pre-term births, and low birth weight infants in comparison to host-country mothers. Therefore, understanding the contextual nuances that play a role in these poor outcomes among refugee populations is very important

The study of antiepileptic activity of clove oil in chemical induced convulsions in mice

Background: The objective was to evaluate and compare the effect of an extract of essential oil of clove with the standard sodium valproate on pentylenetetrazole (PTZ) induced seizures in animal models.Methods: A total of 30 mice were taken, they were given a chemo shock at the concentration of 60 mg/kg using PTZ. 30 mice were divided into 5 groups of 6 animals each the control group received distilled water 5 ml/kg i.p., standard received injection sodium valproate 200 mg/kg i.p. another group received sesame oil – 10 ml/kg i.p. (control), test groups received Clove oil - 0.075 ml/kg i.p., clove oil - 0.1 ml/kg i.p., respectively. All the injections were given 30 mins before the administration of PTZ.Results: Clove oil produced a significant antiepileptic effect at all the doses.Conclusion: Clove oil has shown significant antiepileptic activity in mice

Ewing sarcoma in a child with neurofibromatosis type 1.

We report here on a case of Ewing sarcoma (ES) occurring in a child with neurofibromatosis type 1. The sarcoma had an EWSR1-ERG translocation as well as loss of the remaining wild-type allele of NF1. Loss of the NF1 wild-type allele in the tumor suggests that activation of the Ras pathway contributed to its evolution. Review of available public data suggests that secondary mutations in the Ras pathway are found in ∼3% of ESs. This case suggests that Ras pathway activation may play a role in tumor progression in a subset of ESs

Exclusive breastfeeding in Sri Lanka: problems of interpretation of reported rates

Accurate interpretation of reported breastfeeding rates is essential in understanding the true picture of a country's breastfeeding status. In Sri Lanka, where the reported exclusive breastfeeding (EBF) rate among infants aged from 0 to 5 months is 75%, accurate understanding of this rate is of the utmost importance. The danger of misinterpreting the data and assuming that Sri Lanka has achieved a high EBF rate is that health workers begin to believe that no further effort should be made in this area. This is very dangerous as the potential to further improve rates of EBF will not be addressed. We discuss the interpretation of survey data and various definitions used in the relevant literature. We strongly recommend that interpretation of EBF rates should be done only after careful evaluation of the definitions and survey methods used