Factors influencing the prediction accuracy of model peptides in reversed-phase liquid chromatography

Hydrophobicity is an important physicochemical property of peptides in solution. As well as being strongly associated with peptide stability and aggregation, hydrophobicity governs the solution based chromatographic separation processes, specifically reversed-phase liquid chromatography (RPLC). In addition, hydrophobicity is a major physicochemical property of peptides in comparison to H-bonding, electrostatic, and aromatic properties in intermolecular interactions. However, a wide range of molecular factors can influence peptide hydrophobicity, with accurate predictions depending on specific peptide amino acid compositions, structure, and conformation. It is noticeable that peptide composition, the position of the amino acid, and its neighbouring groups play a crucial role in the elution process. In light of this, the same amino acid behaved differently depending on its position and neighbouring amino acid in the peptide chain. Extra attention should be paid to the denaturation process during the course of elution, as it has been shown to complicate and alter the elution pattern. This paper reports on the key peptide properties that can alter hydrophobicity and, consequently, the RPLC elution behaviour of the peptides, and it will conclude by proposing improved prediction algorithms for peptide elution in RPLC

Service evaluation to establish the sensitivity, specificity and additional value of broad-range 16S rDNA PCR for the diagnosis of infective endocarditis from resected endocardial material in patients from eight UK and Ireland hospitals

Infective endocarditis (IE) can be diagnosed in the clinical microbiology laboratory by culturing explanted heart valve material. We present a service evaluation that examines the sensitivity and specificity of a broad-range 16S rDNA polymerase chain reaction (PCR) assay for the detection of the causative microbe in culture-proven and culture-negative cases of IE. A clinical case-note review was performed for 151 patients, from eight UK and Ireland hospitals, whose endocardial specimens were referred to the Microbiology Laboratory at Great Ormond Street Hospital (GOSH) for broad-range 16S rDNA PCR over a 12-year period. PCR detects the causative microbe in 35/47 cases of culture-proven IE and provides an aetiological agent in 43/69 cases of culture-negative IE. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the 16S rDNA PCR assay were calculated for this series of selected samples using the clinical diagnosis of IE as the reference standard. The values obtained are as follows: sensitivity = 67 %, specificity = 91 %, PPV = 96 % and NPV = 46 %. A wide range of organisms are detected by PCR, with Streptococcus spp. detected most frequently and a relatively large number of cases of Bartonella spp. and Tropheryma whipplei IE. PCR testing of explanted heart valves is recommended in addition to culture techniques to increase diagnostic yield. The data describing the aetiological agents in a large UK and Ireland series of culture-negative IE will allow future development of the diagnostic algorithm to include real-time PCR assays targeted at specific organisms

Early Experience with Ponseti Club Foot Management in Lagos, Nigeria

No Abstract

Multivariate decoding of brain images using ordinal regression.

Neuroimaging data are increasingly being used to predict potential outcomes or groupings, such as clinical severity, drug dose response, and transitional illness states. In these examples, the variable (target) we want to predict is ordinal in nature. Conventional classification schemes assume that the targets are nominal and hence ignore their ranked nature, whereas parametric and/or non-parametric regression models enforce a metric notion of distance between classes. Here, we propose a novel, alternative multivariate approach that overcomes these limitations - whole brain probabilistic ordinal regression using a Gaussian process framework. We applied this technique to two data sets of pharmacological neuroimaging data from healthy volunteers. The first study was designed to investigate the effect of ketamine on brain activity and its subsequent modulation with two compounds - lamotrigine and risperidone. The second study investigates the effect of scopolamine on cerebral blood flow and its modulation using donepezil. We compared ordinal regression to multi-class classification schemes and metric regression. Considering the modulation of ketamine with lamotrigine, we found that ordinal regression significantly outperformed multi-class classification and metric regression in terms of accuracy and mean absolute error. However, for risperidone ordinal regression significantly outperformed metric regression but performed similarly to multi-class classification both in terms of accuracy and mean absolute error. For the scopolamine data set, ordinal regression was found to outperform both multi-class and metric regression techniques considering the regional cerebral blood flow in the anterior cingulate cortex. Ordinal regression was thus the only method that performed well in all cases. Our results indicate the potential of an ordinal regression approach for neuroimaging data while providing a fully probabilistic framework with elegant approaches for model selection

Length- weight relationships, condition factor (K) and relative condition factor (Kn) of Sparids, Dentex congoensis (Maul, 1954) and Dentex angolensis (Maul and Poll, 1953), in Nigerian coastal water

Length-weight relationship and condition factors were estimated for Dentex congoensis and Dentex angolensis of the family sparidae trawled from Nigeria Coastal water in 2009. A total number of 534 specimens ranging from 7.2 – 3.0 cm in total length and 5.4 – 489.8 g in weight were analyzed. The lengthweight relationship is shown by the following equations: LogW –1.610 + 2.791logL (Dentex congoensis) and LogW = -1.558 + 2.776logL (D angolensis). The two species studied exhibited negative allometric growth (b < 3) with the mean b = 2.78 at p < 0.001. The correlation coefficient (R) values were 0.91 (Dentex congoensis) and 0.98 (D angolensis). The condition factor (K) and relative condition factor (Kn) were determined for each species separately. The condition factor (K) obtained for Dentex congoensis and Dentex angolensis were between 0.86 – 8.04 with mean value of 2.48 ± 0.58 and between 2.06 – 6.13 with mean value of 2.79 ± 0.42 respectively. The relative condition factor (Kn) values were 1.28 ±1.09 (Dentex congoensis) and 1.66 ± 2.44 (Dentex anoglensis). The maximum ‘Kn’ values were recorded during the length at first maturity and there was a general decreased in relative condition factor (Kn) with increase length for the two species

Candida albicans as an essential "keystone" component within polymicrobial oral biofilm models?

Background: Existing standardized biofilm assays focus on simple mono-species or bacterial-only models. Incorporating Candida albicans into complex biofilm models can offer a more appropriate and relevant polymicrobial biofilm for the development of oral health products. Aims: This study aimed to assess the importance of interkingdom interactions in polymicrobial oral biofilm systems with or without C. albicans, and test how these models respond to oral therapeutic challenges in vitro. Materials and Methods: Polymicrobial biofilms (two models containing 5 and 10 bacterial species, respectively) were created in parallel in the presence and absence of C. albicans and challenged using clinically relevant antimicrobials. The metabolic profiles and biomasses of these complex biofilms were estimated using resazurin dye and crystal violet stain, respectively. Quantitative PCR was utilized to assess compositional changes in microbial load. Additional assays, for measurements of pH and lactate, were included to monitor fluctuations in virulence “biomarkers.” Results: An increased level of metabolic activity and biomass in the presence of C. albicans was observed. Bacterial load was increased by more than a factor of 10 in the presence of C. albicans. Assays showed inclusion of C. albicans impacted the biofilm virulence profiles. C. albicans did not affect the biofilms’ responses to the short-term incubations with different treatments. Conclusions: The interkingdom biofilms described herein are structurally robust and exhibit all the hallmarks of a reproducible model. To our knowledge, these data are the first to test the hypothesis that yeasts may act as potential “keystone” components of oral biofilms. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Duplication of the EFNB1 Gene in Familial Hypertelorism: Imbalance in Ephrin-B1 Expression and Abnormal Phenotypes in Humans and Mice

Familial hypertelorism, characterized by widely spaced eyes, classically shows autosomal dominant inheritance (Teebi type), but some pedigrees are compatible with X-linkage. No mechanism has been described previously, but clinical similarity has been noted to craniofrontonasal syndrome (CFNS), which is caused by mutations in the X-linked EFNB1 gene. Here we report a family in which females in three generations presented with hypertelorism, but lacked either craniosynostosis or a grooved nasal tip, excluding CFNS. DNA sequencing of EFNB1 was normal, but further analysis revealed a duplication of 937 kb including EFNB1 and two flanking genes: PJA1 and STARD8. We found that the X chromosome bearing the duplication produces ∼1.6-fold more EFNB1 transcript than the normal X chromosome and propose that, in the context of X-inactivation, this difference in expression level of EFNB1 results in abnormal cell sorting leading to hypertelorism. To support this hypothesis, we provide evidence from a mouse model carrying a targeted human EFNB1 cDNA, that abnormal cell sorting occurs in the cranial region. Hence, we propose that X-linked cases resembling Teebi hypertelorism may have a similar mechanism to CFNS, and that cellular mosaicism for different levels of ephrin-B1 (as well as simple presence/absence) leads to craniofacial abnormalities. Hum Mutat 32:1–9, 2011. © 2011 Wiley-Liss, Inc

Exudative pleurisy of coccidioidomycosis: A case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Community-acquired pneumonia is the most common manifestation in primary coccidioides infections (<it>Coccidioides immitis, C. posadasii</it>). It is essential that this endemic dimorphic fungus be considered in order to proceed with the most appropriate diagnostic tools and therapy.</p> <p>Case presentation</p> <p>We present a rare case of primary pleural coccidioides and a review of the current literature for optimal diagnostic methods and therapeutic strategies.</p> <p>Conclusion</p> <p>With increased domestic and international travel, coccidioidomycosis will likely be encountered in nonendemic regions. Recognition by physicians is critical for a timely diagnosis and therapy. Tissue culture can assist in the diagnosis and polymerase chain reaction analysis shows potential as a possible addition.</p

Adjunctive clindamycin for cellulitis: a clinical trial comparing flucloxacillin with or without clindamycin for the treatment of limb cellulitis.

OBJECTIVE: To compare flucloxacillin with clindamycin to flucloxacillin alone for the treatment of limb cellulitis. DESIGN: Parallel, double-blinded, randomised controlled trial. SETTING: Emergency department attendances and general practice referrals within 20 hospitals in England. INTERVENTIONS: Flucloxacillin, at a minimum of 500 mg 4 times per day for 5 days, with clindamycin 300 mg 4 times per day for 2 days given orally versus flucloxacillin given alone. MAIN OUTCOME MEASURES: The primary outcome was improvement at day 5. This was defined as being afebrile with either a reduction in affected skin surface temperature or a reduction in the circumference of the affected area. Secondary outcomes included resolution of systemic features, resolution of inflammatory markers, recovery of renal function, reduction in the affected area, decrease in pain, return to work or normal activities and the absence of increased side effects. RESULTS: 410 patients were included in the trial. No significant difference was seen in improvement at day 5 for flucloxacillin with clindamycin (136/156, 87%) versus flucloxacillin alone (140/172, 81%)-OR 1.55 (95% CI 0.81 to 3.01), p=0.174. There was a significant difference in the number of patients with diarrhoea at day 5 in the flucloxacillin with clindamycin allocation (34/160, 22%) versus flucloxacillin alone (16/176, 9%)-OR 2.7 (95% CI 1.41 to 5.07), p=0.002. There was no clinically significant difference in any secondary outcome measures. There was no significant difference in the number of patients stating that they had returned to normal activities at the day 30 interview in the flucloxacillin with clindamycin allocation (99/121, 82%) versus flucloxacillin alone (104/129, 81%)-adjusted OR 0.90 (95% CI 0.44 to 1.84). CONCLUSIONS: The addition of a short course of clindamycin to flucloxacillin early on in limb cellulitis does not improve outcome. The addition of clindamycin doubles the likelihood of diarrhoea within the first few days. TRIAL REGISTRATION NUMBER: NCT01876628, Results

The detection, survival and persistence of Staphylococcus capitis NRCS-A in neonatal units in England

BACKGROUND: The multi-drug resistant Staphylococcus capitis clone, NRCS-A is increasingly associated with late-onset sepsis in low birthweight newborns in neonatal intensive care units (NICUs) in England and globally. Understanding where this bacterium survives and persists within the NICU environment is key to developing and implementing effective control measures. AIM: To investigate the potential for S. capitis to colonise surfaces within NICUs. METHODS: Surface swabs were collected from four NICUs with and without known NRCS-A colonisations/infections present at the time of sampling. Samples were cultured and S. capitis isolates analysed via whole genome sequencing. Survival of NRCS-A on plastic surfaces was assessed over time and compared to that of non-NRCS-A isolates. The bactericidal activity of commonly used chemical disinfectants against S. capitis was assessed. FINDINGS: Of 173 surfaces sampled, 40 (21.1%) harboured S. capitis with 30 isolates (75%) being NRCS-A. Whilst S. capitis was recovered from surfaces across the NICU, the NRCS-A clone was rarely recovered from outside the immediate neonatal bedspace. Incubators and other bedside equipment were contaminated with NRCS-A regardless of clinical case detection. In the absence of cleaning, S. capitis was able to survive for 3 days with minimal losses in viability (< 0.5 log10 reduction). Sodium troclosene and a QAC-based detergent/disinfectant reduced S. capitis to below detectable levels. CONCLUSION: S. capitis NRCS-A can be readily recovered from the NICU environment, even in units with no recent reported clinical cases of S. capitis infection, highlighting a need for appropriate national guidance on cleaning within the neonatal care environment