Clinical Correlates of the Anatomical Relationships of the Foramen Ovale: A Radioanatomical Study

Introduction Endonasal endoscopic transpterygoid approaches are commonly used techniques to access the infratemporal fossa and parapharyngeal space. Important endoscopic endonasal landmarks for the poststyloid parapharyngeal space, hence the internal carotid artery, include the mandibular nerve at the level of foramen ovale and the lateral pterygoid plate. This study aims to define the anatomical relationships of the foramen ovale, establishing its distance to other important anatomical landmarks such as the pterygoid process and columella. Methods Distances between the foramen ovale, foramen rotundum, and fixed anatomical landmarks like the columella and pterygoid process were measured using computed tomography (CT) scans and cadaveric dissections of the pterygopalatine and infratemporal fossae. Results The mean distances from the foramen ovale to columella and from the foramen rotundum to columella were found to be 9.15 cm and 7.09 cm, respectively. Analysis of radiologic measurements detected no statistically significant differences between sides or gender. Conclusions The pterygoid plates and V3 are prominent landmarks of the endonasal endoscopic approach to the infratemporal fossa and poststyloid parapharyngeal space. A better understanding of the endoscopic anatomy of the infratemporal fossa and awareness of the approximate distances and geometry among anatomical landmarks facilitates a safe and complete resection of lesions arising or extending to these regions.     

Anti-Inflammatory Activity of Fruit Fractions in Vitro,Mediated through Toll-Like Receptor 4 and 2 in the Context of Inflammatory Bowel Disease

Pattern recognition receptors such as Toll-Like Receptor 2 (TLR2) and 4 (TLR4) are important in detecting and responding to stress and bacterial stimuli. Defect or damage in the TLR2 and TLR4 pathways can lead to sustained inflammation, characteristic of inflammatory bowel disease (IBD). The goal of this study was to identify fruit fractions that can be tested further to develop them as complementary therapies for IBD. In order to do this, we identified fruit fractions that mediate their anti-inflammatory response through the TLR4 and TLR2 pathway. Human Embryonic Kidney (HEK)-hTLR4 and hTLR2 cells were stimulated with their respective ligands to induce inflammation. These cells were treated with one of the 12 fractionated fruits and the inflammatory effect measured. 10 of the fruits came up as anti-inflammatory in the hTLR4 assay and nine in the hTLR2 assays. Many of the fruit fractions mediated their anti-inflammatory actions either mainly in their hydrophobic fractions (such as elderberry) or hydrophilic fractions (such as red raspberry), or both. The strongest anti-inflammatory effects were seen for feijoa and blackberry. This study shows that fruits can have multiple fractions eliciting anti-inflammatory effects in a pathway specific manner. This suggests that the compounds found in fruits can act together to produce health benefits by way of reducing inflammation. Exploiting this property of fruits can help develop complimentary therapies for inflammatory diseases.     

Infusion-Related Reaction Following Daptomycin Two-Minute Rapid Intravenous Administration

Background:

Erythroderma, or red man’s syndrome, is a common infusion-related reaction following vancomycin administration. Erythroderma following daptomycin rapid infusion has not been documented.

Objective:

To report a case of erythroderma following daptomycin 2-minute intravenous (IV) injection.

Case Report:

A review of published literature suggests that this is the first published case of a flushing (nonallergic) reaction resulting from a 2-minute IV injection of daptomycin that is not present with standard IV infusion. A 69-year-old woman following right knee reconstructive surgery presented with right knee joint swelling, purulent discharge, and fever. Subsequently, she was diagnosed with a presumed postsurgical infection and was initiated on vancomycin therapy. Following removal of the infected hardware, the patient was discharged and continued outpatient vancomycin therapy. The patient’s renal function began to decline and therapy was discontinued. Daptomycin 6 mg/kg every 48 hours was initiated via 2-minute IV push. On the initial dose, approximately 2 hours post IV infusion, the patient began to notice redness and a warm sensation on her face, neck, and upper part of the chest. Diphenhydramine 25 mg provided limited immediate relief, but all symptoms subsided within 3 to 4 hours. The patient received her next dose 48 hours later over a 40-minute IV infusion with no adverse effects. Subsequent infusions continued at the same dose over 30 minutes for 4 weeks with no further adverse effects.

Conclusion:

A 2-minute intravenous injection of daptomycin in this patient yielded a reaction that was not present on rechallenge with standard, extended infusion.Key Words: daptomycin, erythroderma, rapid infusion, red man’s syndrome, Staphylococcus aureusDaptomycin is a bactericidal lipopeptide antibiotic commonly used for drug-resistant gram-positive pathogens.¹ Daptomycin was originally approved by the US Food and Drug Administration (FDA) in September 2003 as a once-daily 30-minute intravenous (IV) infusion. In November 2010, the FDA approved a 2-minute rapid IV injection based on data from 2 consecutive pharmacokinetic and safety evaluation studies.^2,3 Daptomycin pharmacokinetic parameters were comparable with the 2-minute IV administration group when compared to the 30-minute IV infusion at a dose of 6 mg/kg.⁴ Although rapid infusions offer convenience and potential cost-savings opportunities, there is potential increased risk of infusion-related adverse events. Infusion-related events may include local reactions, such as phlebitis, pain, tenderness, or local erythema, and systemic reactions manifesting as either dermatologic and cardiovascular complications or anaphylaxis. These reactions have been documented with several antimicrobial infusions including ciprofloxacin, amphotericin B, vancomycin, and others agents that stimulate histamine release.⁵ Vancomycin has been classically associated with infusion-related erythroderma or red man’s syndrome. Signs and symptoms of a reaction will often initiate within 1 hour from the start of the infusion.^5,6 For this reason, the preferred infusion rate for vancomycin is no more than 10 mg/min.⁷ In reports to date, local infusion site–related reactions following 2-minute rapid infusion of daptomycin were mild and of short duration, with no systemic flushing reported in the peerreviewed literature. We report a case of an infusion-related reaction with significant flushing secondary to daptomycin following 2-minute IV push that was absent on rechallenge with an extended infusion.     

A window of opportunity for reform in post-conflict settings? The case of Human Resources for Health policies in Sierra Leone, 2002–2012

Background

It is recognized that decisions taken in the early recovery period may affect the development of health systems. Additionally, some suggest that the immediate post-conflict period may allow for the opening of a political ‘window of opportunity’ for reform. For these reasons, it is useful to reflect on the policy space that exists in this period, by what it is shaped, how decisions are made, and what are their long-term implications. Examining the policy trajectory and its determinants can be helpful to explore the specific features of the post-conflict policy-making environment. With this aim, the study looks at the development of policies on human resources for health (HRH) in Sierra Leone over the decade after the conflict (2002–2012).

Methods

Multiple sources were used to collect qualitative data on the period between 2002 and 2012: a stakeholder mapping workshop, a document review and a series of key informant interviews. The analysis draws from political economy and policy analysis tools, focusing on the drivers of reform, the processes, the contextual features, and the actors and agendas.

Findings

Our findings identify three stages of policy-making. At first characterized by political uncertainty, incremental policies and stop-gap measures, the context substantially changed in 2009. The launch of the Free Health Care Initiative provided to be an instrumental event and catalyst for health system, and HRH, reform. However, after the launch of the initiative, the pace of HRH decision-making again slowed down.

Conclusions

Our study identifies the key drivers of HRH policy trajectory in Sierra Leone: (i) the political situation, at first uncertain and later on more defined; (ii) the availability of funding and the stances of agencies providing such funds; (iii) the sense of need for radical change – which is perhaps the only element related to the post-conflict setting. It also emerges that a ‘windows of opportunity’ for reform did not open in the immediate post-conflict, but rather 8 years later when the Free Health Care Initiative was announced, thus making it difficult to link it directly to the features of the post-conflict policy-making environment.

     

The Safety of The Directly Acting Antiviral Treatment For Hepatitis C Virus According To The Egyptian National Program Protocol In Patients With Midrange Ejection Fraction

Background:The Egyptian National Committee of Viral Hepatitis program is the leading national hepatitis C virus (HCV) management program globally. However, limited data is available about the effect of the new directly acting antiviral agents on the cardiovascular system.Objectives:Our study aimed to assess the safety of the relatively new directly acting antiviral agents approved by the National Health Committee in Egypt to treat patients infected with hepatitis C virus who have midrange left ventricular ejection fraction.Methods:This multicenter study included 400 successive patients with an ejection fraction (40–49%) from May 2017 to December 2019. We classified them into two groups: Group I (Child A), who received Sofosbuvir and Daclatasvir for twelve weeks, and Group II (Child B), who received Sofosbuvir, Daclatasvir, and Ribavirin for twelve weeks. Patients were evaluated for their symptoms, ejection fraction, brain natriuretic peptide, lipid profile, fasting blood glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance levels, and Holter monitoring (just before the start of treatment and within three days after completing therapy).Results:We found New York Heart Association Class, ejection fraction, brain natriuretic peptide, premature ventricular contractions burden, as well as highest and lowest heart rate did not show a statistically significant difference in both groups after treatment. The treatment did not cause bradycardia or non-sustained ventricular tachycardia. Fasting blood glucose and fasting insulin levels declined, with improved insulin resistance after treatment in both groups. Both low and high-density lipoprotein cholesterol increased after treatment in Group II.Conclusions:Both regimens of directly acting antiviral agents used in Egypt to treat chronic hepatitis C virus infection are safe in patients with New York Heart Association Class I and II with midrange left ventricular ejection fraction (40–49%). There are beneficial metabolic changes following HCV clearance as an improvement of insulin resistance.     

Thermal transport characterization of carbon and silicon doped stanene nanoribbon: an equilibrium molecular dynamics study

Equilibrium molecular dynamics simulation has been carried out for the thermal transport characterization of nanometer sized carbon and silicon doped stanene nanoribbon (STNR). The thermal conduction properties of doped stanene nanostructures are yet to be explored and hence in this study, we have investigated the impact of carbon and silicon doping concentrations as well as doping patterns namely single doping, double doping and edge doping on the thermal conductivity of nanometer sized zigzag STNR. The room temperature thermal conductivities of 15 nm × 4 nm doped zigzag STNR at 2% carbon and silicon doping concentration are computed to be 9.31 ± 0.33 W m⁻¹ K⁻¹ and 7.57 ± 0.48 W m⁻¹ K⁻¹, respectively whereas the thermal conductivity for the pristine STNR of the same dimension is calculated as 1.204 ± 0.21 W m⁻¹ K⁻¹. We find that the thermal conductivity of both carbon and silicon doped STNR increases with the increasing doping concentration for both carbon and silicon doping. The magnitude of increase in STNR thermal conductivity due to carbon doping has been found to be greater than that of silicon doping. Different doping patterns manifest different degrees of change in doped STNR thermal conductivity. Double doping pattern for both carbon and silicon doping induces the largest extent of enhancement in doped STNR thermal conductivity followed by single doping pattern and edge doping pattern respectively. The temperature and width dependence of doped STNR thermal conductivity has also been studied. For a particular doping concentration, the thermal conductivity of both carbon and silicon doped STNR shows a monotonic decaying trend at elevated temperatures while an opposite pattern is observed for width variation i.e. thermal conductivity increases with the increase in ribbon width. Such comprehensive study on doped stanene would encourage further investigation on the proper optimization of thermal transport characteristics of stanene nanostructures and provide deep insight in realizing the potential application of doped STNR in thermoelectric as well as thermal management of stanene based nanoelectronic devices.

Tunable thermal transport of doped stanene nanoribbon considering the impact of doping concentration, doping pattern, temperature and nanoribbon width.     

Identification of 4-isopropyl–thiotropolone as a novel anti-microbial: regioselective synthesis,NMR characterization,and biological evaluation

We have synthesized and separated tosylated thujaplicin isomers for the first time, and elucidated their structures using 1D, 2D-NMR techniques and X-ray crystallography. The tosylated isomers were used to synthesize 4-isopropyl–thiotropolone and 6-isopropyl–thiotropolone in a regioselective manner. ¹H and ¹³C Chemical shifts of synthesized isomers were fully assigned using several NMR experiments, and their isotropic magnetic shielding was calculated using the GIAO (Gauge Including Atomic Orbitals) method and the B3LYP def2-TZVPP level of theory. The calculated chemical shift values were in a good agreement with the experimental results. The biological activity of all synthesized compounds was evaluated against the fungal pathogen Cryptococcus neoformans and four different bacterial strains (Staphylococcus aureus (ATCC 29213), E. coli (ATCC 35218), Acinetobacter baumannii and Pseudomonas aeruginosa (ATCC 27853)). 4-Isopropyl–thiotropolone was found to inhibit Staphylococcus aureus in a low micro molar range and exhibit good therapeutic index and ADME properties. This compound can be used for future lead optimization to design inhibitors against Staphylococcus aureus (ATCC 29213).

4-Isopropyl–thiotropolone was identified as a novel anti-microbial agent with good therapeutic index and ADME properties.