Phytotherapy for the treatment of Glioblastoma: a review

Background: Phytotherapy; the study of extracts of natural origin in the treatment of disease, has scarcely been applied in the management of GBM. A body of literature exists studying in-vitro, the use of natural extracts against GBM cells. Given persisting poor prognoses, we evaluated, through systematic literature-review the therapeutic potential of naturally sourced extracts in-vivo. Methods: Using OVID, MEDLINE and EMBASE databases were searched with compound search term. Abstracts and full-texts were double-screened by independent reviewers. Results: Nine hundred and eighty-seven articles, excluding duplicated were screened, leading to the inclusion of 14. Amongst murine studies, Ashwagandha, Coptis Chinensis and Fructus Ligustri Lucidi in unprocessed forms, produced significant reductions in tumour volume. Amongst human studies, Perrilyl alcohol, derived from Lavender, reduced angiogenic cytokines in 31% of subjects, halted 6 month disease progression in 48.2% of subjects, and improved mean survival by 4.9 months in separate studies, respectively. Conclusion: Although cursory, current trends in literature demonstrate the value of inhaled Lavender extract in the treatment of GBM, offering tangible clinical benefit to patients receiving conventional treatments. Furthermore, the administration of 8, discrete extracts in mice to produce significant responses in survival and tumour volume, suggest there is further scope for study. Although additional safety tests are required, currently, phytotherapeutics are the crossover to clinical translation, and additional trials are warranted to expound upon thus far promising results

QMLE: a methodology for statistical inference of service demands from queueing data

Estimating the demands placed by services on physical resources is an essential step for the definition of performance models. For example, scalability analysis relies on these parameters to predict queueing delays under increasing loads. In this paper, we investigate maximum likelihood (ML) estimators for demands at load-independent and load-dependent resources in systems with parallelism constraints. We define a likelihood function based on state measurements and derive necessary conditions for its maximization. We then obtain novel estimators that accurately and inexpensively obtain service demands using only aggregate state data. With our approach, and also thanks to approximation methods for computing marginal and joint distributions for the load-dependent case, confidence intervals can be rigorously derived, explicitly taking into account both topology and concurrency levels of the services. Our estimators and their confidence intervals are validated against simulations and real system measurements for two multi-tier applications, showing high accuracy also in the presence of load-dependent resources

Allometric relationships of the dentition of the great White Shark, Carcharodon carcharias, in forensic investigations of shark attacks

As a result of a systematic morphometric study of shark dentitions, a system of notation for describing the location of shark teeth has been developed and is proposed as a standard to be adopted for use in similar studies in the future. The macroscopic morphology of White Shark teeth has been characterised in order to gain quantitative data which might assist in identification of these sharks from bite marks on victims or objects or from shark carcasses. Using these data, a nomogram has been developed which can be used to estimate the body length of a White Shark from measurements of tooth or bite mark morphology. An example of the forensic application of such allometric data is provided as it applied to a recent fatal attack on a diver by a White Shark. This record was migrated from the OpenDepot repository service in June, 2017 before shutting down

Quantitative forensic evaluation of bite marks with the aid of a shape analysis computer program: Part 1; the development of 'SCIP' and the Similarity Index

Bite marks left on human tissue and bitten material have become an important aspect of scientific evidence used for the conviction or acquittal of a suspect. Expert opinion has often been based on subjective comparisons rather than any objective metrical analysis and many experts will agree that there is a need to employ additional comparative tests to achieve unbiased objectivity in their investigation. In this study, an interactive shape analysis computer program ('SCIP' - Shape Comparison Interactive Program) has been employed in an attempt to derive experimentally a quantitative comparison, in the form of a Similarity Index (S.I.), between the 'offender's' teeth and the bite marks produced on a standard flat wax form. The S.I. values obtained using 'SCIP' were evaluated in a variety of experimental bite mark situations. It was found that in no case could the S.I. values produced by comparison of the bite mark with the dental casts from non-perpetrators be confused with the much lower S.I. from comparison of the bite mark with the dental cast of the perpetrator. The use of the Similarity Index derived using the 'SCIP' program is recommended as a simple, accurate and objective means of comparing bite marks in suitable forensic cases. This record was migrated from the OpenDepot repository service in June, 2017 before shutting down

Forensic implications of the variation in morphology of marginal serrations on the teeth of the great white shark

The teeth of the Great White Shark have been examined to ascertain whether there is any commonality in the arrangement or number of the marginal serrations (peaks) or, indeed, whether individual sharks have a unique pattern of shapes or size of the peaks. The teeth of the White Shark are characteristic in size and shape with serrations along almost the entire mesial and distal margins. This study has revealed no consistent pattern of size or arrangement of the marginal serrations that was sufficiently characteristic within an individual shark to serve as a reliable index of identification of a tooth as originating from that particular shark. Nonetheless, the serrations are sufficiently distinctive to enable the potential identification of an individual tooth as having been the cause of a particular bitemark. This record was migrated from the OpenDepot repository service in June, 2017 before shutting down

Carbon turnover in the water-soluble protein of the adult human lens.

PurposeHuman eye lenses contain cells that persist from embryonic development. These unique, highly specialized fiber cells located at the core (nucleus) of the lens undergo pseudo-apoptosis to become devoid of cell nuclei and most organelles. Ostensibly lacking in protein transcriptional capabilities, it is currently believed that these nuclear fiber cells owe their extreme longevity to the perseverance of highly stable and densely packed crystallin proteins. Maintaining the structural and functional integrity of lenticular proteins is necessary to sustain cellular transparency and proper vision, yet the means by which the lens actually copes with a lifetime of oxidative stress, seemingly without any capacity for protein turnover and repair, is not completely understood. Although many years of research have been predicated upon the assumption that there is no protein turnover or renewal in nuclear fiber cells, we investigated whether or not different protein fractions possess protein of different ages by using the (14)C bomb pulse.MethodsAdult human lenses were concentrically dissected by gently removing the cell layers in water or shaving to the nucleus with a curved micrometer-controlled blade. The cells were lysed, and the proteins were separated into water-soluble and water-insoluble fractions. The small molecules were removed using 3 kDa spin filters. The (14)C/C was measured in paired protein fractions by accelerator mass spectrometry, and an average age for the material within the sample was assigned using the (14)C bomb pulse.ResultsThe water-insoluble fractions possessed (14)C/C ratios consistent with the age of the cells. In all cases, the water-soluble fractions contained carbon that was younger than the paired water-insoluble fraction.ConclusionsAs the first direct evidence of carbon turnover in protein from adult human nuclear fiber cells, this discovery supports the emerging view of the lens nucleus as a dynamic system capable of maintaining homeostasis in part due to intricate protein transport mechanisms and possibly protein repair. This finding implies that the lens plays an active role in the aversion of age-related nuclear (ARN) cataract

Community-linked maternal death review (CLMDR) to measure and prevent maternal mortality: a pilot study in rural Malawi.

In Malawi, maternal mortality remains high. Existing maternal death reviews fail to adequately review most deaths, or capture those that occur outside the health system. We assessed the value of community involvement to improve capture and response to community maternal deaths

Knowledge and perceptions of quality of obstetric and newborn care of local health providers: A cross-sectional study in three districts in Malawi

AimQuality of service delivery for maternal and newborn health in Malawi isinfluenced by human resource shortages and knowledge and care practicesof the existing service providers. We assessed Malawian healthcareproviders’ knowledge of management of routine labour, emergencyobstetric care and emergency newborn care; correlated knowledgewith reported confidence and previous study or training; and measuredperception of the care they provided.MethodsThis study formed part of a large-scale quality of care assessment inthree districts (Kasungu, Lilongwe and Salima) of Malawi. Subjects wereselected purposively by their role as providers of obstetric and newborncare during routine visits to health facilities by a research assistant. Researchassistants introduced and supervised the self-completed questionnaire bythe service providers. Respondents included 42 nurse midwives, 1 clinicalofficer, 4 medical assistants and 5 other staff. Of these, 37 were staffworking in facilities providing Basic Emergency Obstetric Care (BEMoC)and 15 were from staff working in facilities providing ComprehensiveEmergency Obstetric Care (CEMoC).ResultsKnowledge regarding management of routine labour was good (80%correct responses), but knowledge of correct monitoring during routinelabour (35% correct) was not in keeping with internationally recognizedgood practice. Questions regarding emergency obstetric care were  answered correctly by 70% of respondents with significant variation depending on clinicians’ place of work. Knowledge of emergency newborn care was poor across all groups surveyed with 58% correct responses and high rates of potentially life-threatening responses from BEmOC facilities. Reported confidence and training had little impact on levels of knowledge. Staff in general reported perception of poor quality of care.ConclusionSerious deficiencies in providers’ knowledge regarding monitoring duringroutine labour and management of emergency newborn care weredocumented. These may contribute to maternal and neonatal deaths inMalawi. The knowledge gap cannot be overcome by simply providingmore training

Designing of promising Tromethamine-Diflunisal-Pyrrole combinations based on COX binding, drug-properties and safety

Gastric issues that accompany the use of NSAIDs (Non-steroid anti-inflammatory drugs) are always a serious global concern. The inhibition of the Cycloxygenase enzyme (COX) limits the prostaglandin synthesis and thereby facilitates the control of pains, inflammation etc. But this creates gastric issues due to the reduction of mucin formation in the stomach. The present work was performed to create a modification in the structure of NSAID drug Diflunisal, to reduce the gastric effect of acidic moiety in the structure and elevate the overall biological properties. The drug Tromethamine, a base used in acidosis treatment was substituted to reduce the acidic issues. The heterocyclic compound pyrrole was substituted to elevate the properties. Neutral, salt, amide and ester combinations of Tromethamine-Diflunisal were designed, optimized and docked to the crystal structures of COX-1 (PDB ID: 6Y3C) and COX-2 (PDB ID: 5IKR) enzymes, using PyRx software. The combinations with lower COX-1 and COX-2 binding energies relative to Diflunisal were noted. It was analysed if the combinations of Diflunisal, Tromethamine and pyrrole lowers drug-properties or induce toxicities. Pyrrole substitution at position R4 was not found favourable for COX binding. Among the favourable combinations, DF19 is the Diflunisal-Pyrrole-Tromethamine combination, equally favourable for binding to COX targets