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Objective: The aim of this study was to review and summarize the effects of nasoalveolar molding (NAM) therapy published in the most recent literature. Method: A search were conducted from “nasoalveolar molding,” “nasoalveolar molding Grayson,” and “nasolabial esthetics”. The articles were then subdivided into case reports, editorials/expert opinions, and traditional prospective and retrospective studies Results: In order to summarize the results of the literature review, the discussion section was organized into three primary categories. The first of these categories deals with the burden of treatment to the NAM patient and the caregiver, the psychological and monetary effect on the caregiver(s), and the effect of NAM treatment on the number of surgeries required. The second category deals primarily with the specific treatment effects seen as a result of NAM therapy, such as the improvement of nasal symmetry and lengthening of the columella, as well as studies that compare NAM treated patients to non-NAM treated and normal controls. Lastly, we have included a brief summary of alternative methods to NAM therapy, including the recent use of CAD/CAM technology in NAM therapy. Conclusions: Based on the current literature, NAM does indeed show significant improvements in nasolabial esthetics and increases columellar length. It is shown to have positive psychosocial outcomes and lower cost for caregivers via reduction of future surgeries. Finally, technological advancements are allowing for streamlined NAM fabrication.

Abstract Background Neospora caninum has been documented to infect most domestic wildlife but is known to primarily infect dogs and cattle and is considered an important cause of abortion in camels. Objective The aim of this study was to estimate the molecular detection of Neospora caninum in tissues of naturally infected camelids. Methods Brain, tongue (bottom and tip) and masseter muscles from 35 slaughtered camelids from Tataouine and Médenine regions were collected (n = 140 samples). PCR was used to amplify and detect N. caninum DNA in tissues samples followed by sequencing of some PCR products. A phylogenetic tree was then constructed to compare the partial sequences of the ITS1 gene with GenBank sequences. Histopathology examination was used to detect Neospora spp. cysts, but no lesions were observed. Results The overall molecular detection of N. caninum in camelids was 34.3% (12/35). The highest molecular detection of N. caninum was recorded in animals of more than 3 years old (6/9) and in animals aged between 1 and 3 years old (4/12). Whilst, the lowest molecular detection (2/14) was observed in animals 1 year or younger (p = 0.035). There were no significant differences in molecular detection of N. caninum according to both locality and gender (p > 0.05). Similarly, there was no difference of prevalence between different anatomical locations. Comparison of the partial sequences of the ITS1 gene revealed 100–95.5% similarity among our N. caninum amplicon (MW551566) and those deposited in GenBank. Conclusion These results highlight the presence of a risk infection by N. caninum in camels. For preventing N. caninum infection further studies are needed to improve our knowledge about the epidemiology of neosporosis in North Africa.

A right-handed man in his early 60s with hypertension controlled by a single prescription medication presented with left-sided heaviness and intermittent right occipital headache. Initial diagnostic workup was unremarkable. CT revealed an enhancing lesion located in the right parietal lobe, with mild mass effect on the right occipital horn, indicative of a brain abscess. The patient was initially treated with a course of empirical antibiotics, including ceftriaxone, vancomycin, metronidazole and dexamethasone. The neurosurgery team aspirated the abscess the following day and extracted yellow pus that was sampled for bacterial and fungal cultures. These cultures returned positive for Rhinocladiella mackenziei , prompting a discontinuation of the empirical antibiotics and initiation of intravenous liposomal amphotericin B for 4 weeks. Intravenous posaconazole was added to the patient's existing therapy regimen, which was substituted with oral isavuconazole on discharge. The patient continues to take isavuconazole, and follow-up imaging has demonstrated regression of the abscess., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives To assess the general public's level of knowledge on glaucoma and cataract and measure their ability to differentiate between the two. Materials and methods This was an analytic, cross-sectional study. We used a self-explanatory questionnaire to obtain information regarding the level of knowledge of glaucoma and cataract and measured the ability of the public to differentiate between the two in Saudi Arabia. The obtained results were manually entered into an Excel sheet and analyzed using the Statistical Package for the Social Sciences (SPSS) software version 26. Results The levels of knowledge on glaucoma and cataract and those of education were significantly associated (chi-square: P < 0.001). There was a significant association between having an eye condition and the ability to correctly define glaucoma and cataract (chi-square: P = 0.002). Concerning the definition of glaucoma, 48.4% of the participants who had a previous eye disorder answered correctly, whereas 40.1% of the participants who had no previous eye disorder answered correctly. In addition, 20.9% of the participants with a previous eye disease and 17.6% of the participants without any previous eye disease defined glaucoma incorrectly as cataract. A total of 71.4% of the participants with a previous eye disease, compared with 49.6% of the participants without any previous eye disease, correctly defined cataract. In addition, only 7.3% of the participants with a history of eye disease answered the definition of cataract as that of glaucoma (glaucoma: chi-square, P = 0.002; cataract: chi-square, P < 0.001). Conclusion This study is in line with other studies measuring the knowledge of the two diseases, with glaucoma being less known than cataract. While many of the participants were able to define glaucoma and cataract, they had many difficulties identifying how they present and which symptom belonged to cataract and glaucoma. Glaucoma and cataract were confused by a number of participants especially in the case of glaucoma as more defined it as cataract rather than the opposite., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Alammar et al.)

Gamma irradiation is a useful technology for degrading mycotoxins. The purpose of this study was to investigate the effect of irradiation on ochratoxin A (OTA) stability under different conditions. OTA was irradiated in methanolic solution and on millet flour at doses of 2 and 4 kGy. Residual OTA concentrations and possible degradation products in irradiated samples were analyzed by high-performance liquid chromatography with fluorescence detection and liquid chromatography coupled to mass spectrometry. The extent of in vitro cytotoxicity of OTA to HepG2 cells, with and without irradiation treatment, was assessed with an MTT assay. OTA was more sensitive to gamma radiation on Tunisian millet flour than in methanolic solutions. After irradiation of naturally contaminated millet flour, the OTA concentration was significantly reduced by 48 and 62% at a dose of 2 and 4 kGy, respectively. However, in the methanolic solution, OTA at concentrations of 1 and 5 μg mL -1 was relatively stable even at a dose of 4 kGy, with no degradation products detected in the chemical analysis. Analytical results were confirmed by cell culture assays. The remaining cytotoxicity (MTT assay) of OTA following irradiation was not significantly affected compared with the controls. These findings indicate that gamma irradiation could offer a solution for OTA decontamination in the postharvest processing chain of millet flour. However, the associated toxicological hazard of decontaminated food matrices needs more investigation.

Background: The aim of this study was to determine the utility of dried blood spots (DBS) compared with conventional plasma collection methods for characterization of efavirenz pharmacokinetics, in the setting of a large-scale, global clinical trial (ENCORE1)., Methods: Six hundred thirty patients were recruited from 38 sites and had single matched whole blood DBS and plasma samples (mid-dose interval) taken at weeks 4 and 12 of treatment. In addition, a subgroup of patients underwent intensive DBS and plasma sampling (0-24 hours) to provide full-profile data for pharmacokinetic parameters. Efavirenz concentrations were determined by validated high-performance liquid chromatography-mass spectrometry methods. A DBS-predicted plasma concentration was derived and linear regression and Bland-Altman plots were used to compare DBS-predicted plasma concentrations with that of measured plasma concentrations., Results: Efavirenz DBS and plasma concentrations were significantly correlated (R = 0.904, P < 0.001; n = 1094), and DBS concentrations were, on average, 53% ± 9.5% lower than plasma. In the main study, the DBS-predicted plasma values significantly underestimated the true measured concentration of efavirenz in plasma; the mean difference (95% confidence interval) between efavirenz DBS-predicted concentrations and measured plasma concentrations was -0.451 mg/L (-0.504 to -0.398) at week 4 (n = 561). However, in the intensive study, the mean difference was only 0.086 mg/L (-0.006 to 0.178) at 12 hours after dose (n = 46) and was not statistically significant., Conclusions: Our data show a high correlation between measurements of efavirenz concentrations in plasma and in DBS. However, DBS concentrations significantly underestimated the true measured plasma concentrations in the sparse samples taken in this large multinational ENCORE1 trial.

Aims and Objectives: The objective of the present investigation is to evaluate patients' pain perception and discomfort, the duration of pain and the level of self-medication over time during tooth separation, and the effectiveness of elastomeric and spring types of orthodontic separators in Saudi population., Materials and Methods: The study group consisted of 30 female adolescent patients who had elastomeric/spring separators as part of their orthodontic treatment. A self-administrated questionnaire comprising 16 multiple choice questions and another with visual analog scale were used to record the patient's pain perceptions at 4 hours, 24 hours, 3 days, 5 days, and 7 days from the time of insertion. The level of pain and discomfort during these time periods were assessed by a visual analog scale. After a separation period of 7 days, the amount of separation was measured with a leaf gauge. Type and frequency of analgesic consumption was also recorded. The Statistical Package for the Social Sciences (SPSS) version 20 (IBM SPSS -Chicago, IL: SPSS Inc.,) was used for statistical analysis., Results: The data showed significant increase in the level of pain at 4 hours, 24 hours, and 3 days from separator placement. The elastomeric separators produced significantly more separation than the spring separators and also caused maximum pain during the first 3 days after insertion. However, there was no significant difference between the score of pain between two separators at all time intervals., Conclusion: Both elastomeric and spring separators showed comparative levels of pain and discomfort during the early phase of separation. Elastomeric separators were found to be more effective in tooth separation than spring separators. However, further studies are necessary to substantiate this preliminary observation., Competing Interests: There are no conflicts of interest.

Hydrotalcite (HT), also known as a layered double hydroxide (LDH) compound, has been widely used in past years in the formulation of drugs due to its specific properties including good biocompatibility, null toxicity, high chemical stability and pH-dependent solubility which aid in drug controlled release. In this work, berberine chloride (BBC) class antibacterial agent was immobilized into magnesium-aluminum LDH in order to improve the drug efficiency as well as to achieve the controlled release property. BBC molecules were immobilized into MgAl LDH through a conventional ion exchange reaction and co-precipitation method. The ion-exchange experiments of BBC on MgAl LDH were investigated with particular attention paid to the influence of the layer charge, the nature of the intercalated anion and the morphology. The immobilization efficiency was dependent upon the LDH properties and the immobilization process. Characterization by powder x-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy and contact angle measurements revealed that the interaction of BBC with MgAl LDH occurs by adsorption rather than intercalation of BBC within LDH layers. In vitro anti-bacterial tests were carried out using disc diffusion assay to prove the effectiveness of these novel biohybrid beads as a controlled drug delivery method. Consequently, the BBC-LDH co-precipitated formulation revealed an enhanced anti-bacterial activity compared to the ion-exchanged formulation not only due to an improvement of chemical stability and retained amount of BBC molecules but also due to the release property., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Efavirenz (EFV) is one of the preferred components of first-line antiretroviral treatment. EFV is characterized by a long plasma half-life (40-55 hours) with large interpatient variability, which raises the potential for individualization of therapy. Analyses of EFV levels in plasma require specialized facilities (cold storage/transport) which, in resource-limited settings, can be problematic; dried blood spots (DBS)-EFV measurements thus provide a cheap easy alternative for therapeutic drug monitoring. Our aim was to develop and validate a liquid chromatography-mass spectrometry method to quantify EFV in DBS collected as part of clinical trials in resource-limited settings., Methods: DBS for standards, quality control samples, and patient samples were excised and then extracted with ethyl acetate/n-hexane (50/50 vol/vol) after addition of internal standard hexobarbital, and 1 mol/L K2CO3. The extract was evaporated to dryness, the residue reconstituted in mobile phase and analyzed directly by liquid chromatography-mass spectrometry. Gradient elution was on a reverse-phase C18 column using 1 mmol/L ammonium acetate in water and acetonitrile. Quantification was by selected reaction monitoring in negative ionization mode. DBS samples were obtained at several time points over 24 hours from HIV+ patients on either 400 or 600 mg EFV in combination with emtricitabine/tenofovir., Results: The internal standard and EFV eluted at 2.68 and 3.54 minutes, respectively in a 5-minute run time. Matrix effects were minimal (-5.4%). Calibration curves were validated over a concentration range of 25-5000 ng/mL. Intra-assay and interassay variations ranged between 6.7% and 8.7% for imprecision and 100.3% and 104.2% for accuracy. Mean recovery was >64%. The DBS data showed a strong positive correlation with a validated plasma EFV assay (R = 0.9764, P < 0.001). EFV concentrations from DBS were approximately 42% lower than the paired plasma values, and the ratio of blood/plasma did not change over the dosing interval., Conclusions: The validated assay is now routinely applied to clinical samples measuring DBS EFV for pharmacokinetic analysis. The methodology is robust, accurate, and sensitive.

Background: The diagnostic and prognostic assessments of infective endocarditis (IE) are challenging. To investigate the host response during IE and to identify potential biomarkers, we determined the circulating gene expression profile using whole genome microarray analysis., Methods and Results: A transcriptomic case-control study was performed on blood samples from patients with native valve IE (n = 39), excluded IE after an initial suspicion (n = 10) at patient's admission, and age-matched healthy controls (n = 10). Whole genome microarray analysis showed that patients with IE exhibited a specific transcriptional program with a predominance of gene categories associated with cell activation as well as innate immune and inflammatory responses. Quantitative real-time RT-PCR performed on a selection of highly modulated genes showed that the expression of the gene encoding S100 calcium binding protein A11 (S100A11) was significantly increased in patients with IE in comparison with controls (P<0.001) and patients with excluded IE (P<0.05). Interestingly, the upregulated expression of the S100A11 gene was more pronounced in staphylococcal IE than in streptococcal IE (P<0.01). These results were confirmed by serum concentrations of the S100A11 protein. Finally, we showed that in patients with IE, the upregulation of the aquaporin-9 gene (AQP9) was significantly associated with the occurrence of acute heart failure (P = 0.02)., Conclusions: Using transcriptional signatures of blood samples, we identified S100A11 as a potential diagnostic marker of IE, and AQP9 as a potential prognostic factor.

Coxiella burnetii, the causative agent of Q fever, has evolved a wealth of mechanisms in order to persist within hosts. Two tissues, namely adipose tissue and placenta, are candidates to house C. burnetii, but the mechanisms governing C. burnetii survival in these tissues are still unknown. In contrast, monocytes and macrophages are well-known targets of C. burnetii. First, C. burnetii has developed a specific strategy of phagocytosis subversion that consists of the inhibition of integrin interplay. Second, C. burnetii persistence is associated with macrophage activation profiles. Indeed, monocytes (in which C. burnetii survives without replication) exhibit a proinflammatory M1-type response, whereas macrophages (in which C. burnetii slowly replicates) are polarized towards an M2-type. Third, interleukin-10 produced by monocytes is a main factor of the chronic development of Q fever, and murine models confirm the key role of interleukin-10 in C. burnetii persistence. Fourth, apoptotic cells may play a key role in chronic Q fever. The uptake of apoptotic cells by circulating monocytes increases C. burnetii replication by redirecting monocytes toward a non-protective M2 profile. In the presence of interferon-γ, apoptotic cell engulfment is inhibited and monocytes polarized toward an M1 program are able to kill C. burnetii; this is the situation observed in patients with uncomplicated acute Q fever. Finally, we cannot exclude that regulatory T cells may play a role in C. burnetii persistence because their number is increased in patients with chronic Q fever.

Background: Angiotensin-converting enzyme inhibitors in native nephropathies reduce proteinuria and delay progression to renal failure. Data in renal transplantation remain limited. A negative effect on glomerular filtration rate was concluded in a recent systematic review., Methods: In this novel randomized controlled trial, 47 patients with chronic allograft nephropathy, severe renal impairment, and more than or equal to 1 g/24 hr proteinuria were randomized to lisinopril (group A) or other hypotensives (group B) for 1 year. Sodium bicarbonate was given to all patients to treat metabolic acidosis prophylactically (acidosis increases significantly with lisinopril). The annual rate of decline of graft function was measured isotopically (primary outcome) and 24 hr proteinuria, genotyping, radiolabeled polypeptide aprotinin proximal tubular catabolic studies (in group A only) as secondary outcome measurements were undertaken., Results: At baseline, groups were comparable except for greater proteinuria in group A. After 1 year, the rate of decline of graft function and graft survival were comparable in both groups. Proteinuria decreased significantly in group A patients only. Lisinopril also significantly reduced radiolabeled aprotinin uptake and metabolism, plasma aldosterone, and ammonia excretion. Plasma potassium, bicarbonate, and mean arterial pressures were comparable in both groups. Patients with more than or equal to 30% reduction in proteinuria had a significant association with rs699 polymorphism in the angiotensinogen gene., Conclusions: The rate of decline of renal graft function in patients with chronic allograft nephropathy was not adversely affected by lisinopril therapy given for 1 year. Lisinopril significantly reduced proteinuria, renal proximal tubular polypeptide catabolism, plasma aldosterone, and ammonia excretion suggesting relative preservation of graft function. Treating metabolic acidosis allowed safe and prolonged use of angiotensinogen-converting enzyme inhibitors.

Proteinuria is pathogenic to proximal tubular cells (PTC) and linked with progression to renal failure. The aim of this study was to determine the effects of human serum albumin (HSA) overload on the changes in gene and protein expression stimulated by oxidative stress in PTC and any interaction with ANG II that is pivotal in disease pathogenesis. Markers of oxidative stress, antioxidant defences, transcription factor activation, and the expression of stress-related genes were measured in human PTC (HK-2 cells) overloaded with either globulin-free fatty acid free (GF/FAF) HSA or globulin-free (GF) HSA. The effects of ANG II were also determined. HSA overload in HK-2 cells caused PTC hyperfunction, increased oxidative stress, and an upregulation of adaptive responses and stress-related genes. Some responses were common to both HSAs but others were unique to either HSA and unaffected by addition of ANG II or candesartan (a specific ANG II type 1 receptor blocker). ANG II also independently induced oxidative stress and upregulated other stress-related genes. HSA overload in HK-2 cells stimulated increased oxidative stress and upregulated changes in stress-related gene expression indicating new pathways of PTC injury that are not mediated via ANG II type 1 receptors.

Background: Chronic allograft nephropathy (CAN) is commonly associated with proteinuria. In native nephropathies, proteinuria is linked with proximal renal tubular damage. This study uses regression analysis to link proteinuria with urinary N-acetyl-beta-d-glucosaminidase (NAG) as a marker of tubular injury or hyperfunction in renal transplant patients., Methods: Proteinuria and urinary NAG were measured and regression analysis applied in 105 transplant patients (42 with CAN). Most were receiving calcineurin inhibitor-based immunosuppression (cyclosporine, n=60; tacrolimus, n=26; and neither drug, n=19). Patients with native nephropathies (n=96) and volunteers (n=21) were also studied., Results: Urinary NAG increased with increasing proteinuria. However, patients taking calcineurin inhibitors had higher urinary NAG at any level of urinary protein than those on alternative therapy, or in native nephropathies., Conclusions: In groups of transplant patients taking different immunosuppressive regimens, regression analysis of urinary NAG against urinary protein can identify the separate effects of drug-related tubular injury or hyperfunction from that of proteinuria.

Background: Electrospray ionization mass spectrometry (ESIMS) has been successfully applied to the identification of hemoglobin (Hb) variants and the presence of glucose adducts (mass difference of 162 Da) on the separate Hb alpha and beta chains. To establish the potential of ESIMS as a routine and/or a reference method for the quantification of glycohemoglobin (HbA1c), we carried out a detailed evaluation over a 4-month period in a routine laboratory environment., Methods: We optimized a procedure using ESIMS suitable for the routine quantitative analysis of HbA1c. We determined reliability and reproducibility over 4 months and assessed the potential for automated sample injection. We then compared values of 1022 blood samples from diabetic patients with a routine HPLC-based ion-exchange procedure (HA-8140; Menarini)., Results: Results of HbA1c measurement by ESIMS were available within 3 min. The analytical imprecision (CV) was 1.6-5.0% for both manual and automated injections. Data collection over the m/z 980-1400 range confirmed lower glycation of the alpha chain relative to the beta chain (0.66:1). Only one glycation was observed per globin chain. The overall glycohemoglobin (i.e., the average of alpha- and beta-chain glycations) measured by ESIMS (x) on 1022 blood samples was lower than by HPLC (y): y = 1.0432x + 0.4815. However, the ss-chain glycation measured by ESIMS was up to 20% higher than the value measured by ion-exchange HPLC and showed a close conformity, particularly at 5-10% HbA1c, with the ion-exchange Diabetes Control and Complications Trial (DCCT)-corrected and the United Kingdom National External Quality Assessment Scheme DCCT mean return values., Conclusions: ESIMS provides a precise measurement of HbA1c and, in particular, glycation of the beta chain. The method is robust and could be proposed as a procedure to substantiate HbA1c measurement and/or calibration.