Parsonage-Turner Syndrome With an Uncommon Trigger: A Case Study and Literature Review.

Patients with Parsonage-Turner syndrome (PTS) are often misdiagnosed due to overlapping symptoms with other conditions and coinciding procedures. Because it is most commonly seen following viral infection, it is often not considered in other cases. We present a rare case in which a 79-year-old female, with no significant past medical history, was diagnosed with PTS two months after a biopsy of the right levator scapulae muscle. Forty-eight hours after the procedure, she developed sudden-onset pain and weakness in the right scapulae and neck, followed by worsened weakness. This case report highlights the importance of considering PTS before proceeding with treatment. Patients with suspected PTS should undergo electromyography (EMG) to confirm diagnosis and monitor disease progression and resolution.

Inhibition of angiotensin II type 1 receptor agonistic autoantibodies by direct binding does not impact reduced uterine perfusion pressure offspring birthweight and blood pressure at adulthood.

BACKGROUND: Preeclampsia, a new-onset hypertension with end-organ damage in pregnancy, is associated with maternal death and morbidity, low birthweight, and B cells producing agonistic autoantibodies to the angiotensin II type 1 receptor. Angiotensin II type 1 receptor agonistic autoantibodies are produced during pregnancy and after delivery and are in the fetal circulation of women with preeclampsia. Angiotensin II type 1 receptor agonistic autoantibodies are shown to contribute to endothelial dysfunction, renal dysfunction, hypertension, fetal growth restriction, and chronic inflammation in women with preeclampsia. The reduced uterine perfusion pressure rat model of preeclampsia exhibits these features. In addition, we have shown that the administration of a 'n7AAc', which blocks the actions of the angiotensin II type 1 receptor autoantibodies, improves preeclamptic features in the rat with reduced uterine perfusion pressure. However, the effect of a 'n7AAc' on the long-term health of the offspring of rats with reduced uterine perfusion pressure is unknown. OBJECTIVE: This study aimed to test the hypothesis that inhibition of angiotensin II type 1 receptor autoantibodies during pregnancy will improve offspring birthweight and prevent increased cardiovascular risk in offspring in adulthood. STUDY DESIGN: To test our hypothesis, a 'n7AAc' (24 µg/d) or vehicle (saline) was given on gestation day 14 via miniosmotic pumps to sham-operated (sham) and Sprague-Dawley rat dams with reduced uterine perfusion pressure. Dams were allowed to deliver naturally, and pup weights were recorded within 12 hours after birth. Pups were aged to 16 weeks, at which time mean arterial pressure was measured and whole blood was collected to measure immune cells by flow cytometry, cytokines by enzyme-linked immunosorbent assay, and angiotensin II type 1 receptor autoantibodies by bioassay. A 2-way analysis of variance with the Bonferroni multiple comparison posthoc test was used for statistical analysis. RESULTS: There was no significant change in offspring birthweight of 'n7AAc'-treated male (5.63±0.09 g) or female (5.66±0.14 g) offspring from reduced uterine perfusion pressure dams compared with vehicle male (5.51±0.17 g) or female (5.74±0.13 g) offspring from reduced uterine perfusion pressure dams. In addition, 'n7AAc' treatment did not affect the birthweight of sham male (5.83±0.11 g) or female (5.64±0.12) offspring compared with vehicle sham male (5.811±0.15 g) or female (5.40±0.24 g) offspring. At adulthood, mean arterial pressure was unchanged in 'n7AAc' treated-male (133±2 mm Hg) and female (127±3 mm Hg) offspring from reduced uterine perfusion pressure dams compared with vehicle male (142±3 mm Hg) and female (133±5 mm Hg) offspring from reduced uterine perfusion pressure dams, the 'n7AAc'-treated sham male (133±3 mm Hg) and female (135±3 mm Hg) offspring, and vehicle sham male (138±4 mm Hg) and female (130±5 mm Hg) offspring. The circulating angiotensin II type 1 receptor autoantibodies were increased in vehicle male (10±2 ΔBPM) and female (14±2 ΔBPM) offspring from reduced uterine perfusion pressure dams and 'n7AAc'-treated male (11±2 ΔBPM) and female (11±2 ΔBPM) offspring from reduced uterine perfusion pressure dams compared with vehicle sham male (1±1 ΔBPM) and female (-1±1 ΔBPM) offspring and 'n7AAc'-treated sham male (-2±2 ΔBPM) and female (-2±2 ΔBPM) offspring. CONCLUSION: Our findings indicated that perinatal 7-amino acid sequence peptide treatment does not negatively impact offspring survival or weight at birth. Perinatal 'n7AAc' treatment did not prevent increased cardiovascular risk in offspring, but it also did not cause an increased cardiovascular risk in offspring with reduced uterine perfusion pressure compared with controls. Furthermore, perinatal 'n7AAc' treatment did not affect endogenous immunologic programming as observed by no change in circulating angiotensin II type 1 receptor autoantibodies in either sex of adult offspring from reduced uterine perfusion pressure dams.

Intrarenal Dopaminergic System Is Dysregulated in SS-Resp18mutant Rats.

The genetic and molecular basis of developing high blood pressure and renal disease are not well known. Resp18mutant Dahl salt-sensitive (SS-Resp18mutant) rats fed a 2% NaCl diet for six weeks have high blood pressure, increased renal fibrosis, and decreased mean survival time. Impairment of the dopaminergic system also leads to hypertension that involves renal and non-renal mechanisms. Deletion of any of the five dopamine receptors may lead to salt-sensitive hypertension. Therefore, we investigated the interaction between Resp18 and renal dopamine in SS-Resp18mutant and Dahl salt-sensitive (SS) rats. We found that SS-Resp18mutant rats had vascular dysfunction, as evidenced by a decrease in vasorelaxation in response to sodium nitroprusside. The pressure-natriuresis curve in SS-Resp18mutant rats was shifted down and to the right of SS rats. SS-Resp18mutant rats had decreased glomerular filtration rate and dopamine receptor subtypes, D1R and D5R. Renal dopamine levels were decreased, but urinary dopamine levels were increased, which may be the consequence of increased renal dopamine production, followed by secretion into the tubular lumen. The increased renal dopamine production in SS-Resp18mutant rats in vivo was substantiated by the increased dopamine production in renal proximal tubule cells treated with L-DOPA. Overall, our study provides evidence that targeted disruption of the Resp18 locus in the SS rat dysregulates the renal dopaminergic system.

Inhibition of the AT1R agonistic autoantibody in a rat model of preeclampsia improves fetal growth in late gestation.

Placenta ischemia, the initiating event in preeclampsia (PE), is associated with fetal growth restriction. Inhibition of the agonistic autoantibody against the angiotensin type 1 receptor AT1-AA, using an epitope-binding inhibitory peptide ('n7AAc') attenuates increased blood pressure at gestational day (G)19 in the clinically relevant reduced uterine perfusion pressure (RUPP) model of PE. Thus we tested the hypothesis that maternal administration of 'n7AAc' does not transfer to the fetus, improves uterine blood flow and fetal growth, and attenuates elevated placental expression of miRNAs implicated in PE and FGR. Sham or RUPP surgery was performed at G14 with vehicle or 'n7AAc' (144 µg/day) administered via an osmotic pump from G14 to G20. Maternal plasma levels of the peptide on G20 were 16.28 ± 4.4 nM, and fetal plasma levels were significantly lower at 1.15 ± 1.7 nM (P = 0.0007). The uterine artery resistance index was significantly elevated in RUPP (P < 0.0001) but was not increased in 'n7AAc'-RUPP or 'n7AAc'-Sham versus Sham. A significant reduction in fetal weight at G20 in RUPP (P = 0.003) was not observed in 'n7AAc'-RUPP. Yet, percent survival was reduced in RUPP (P = 0.0007) and 'n7AAc'-RUPP (P < 0.0002). Correlation analysis indicated the reduction in percent survival during gestation was specific to the RUPP (r = 0.5342, P = 0.043) and independent of 'n7AAc'. Placental miR-155 (P = 0.0091) and miR-181a (P = 0.0384) expression was upregulated in RUPP at G20 but was not elevated in 'n7AAc'-RUPP. Collectively, our results suggest that maternal administration of 'n7AAc' does not alter fetal growth in the RUPP implicating its potential as a therapeutic for the treatment of PE.NEW & NOTEWORTHY The seven amino acid inhibitory peptide to the AT1-AA ('n7AAc') has limited transfer to the fetus at gestational day 20, improves uterine blood flow and fetal growth in the reduced uterine perfusion pressure model of preeclampsia (PE), and does not impair fetal survival during gestation in sham-operated or placental ischemic rats. Collectively, these findings suggest that maternal administration of 'n7AAc' as an effective strategy for the treatment of PE is associated with improved outcomes in the fetus.

Paraoxonase-1 Regulation of Renal Inflammation and Fibrosis in Chronic Kidney Disease.

Papraoxonase-1 (PON1) is a hydrolytic lactonase enzyme that is synthesized in the liver and circulates attached to high-density lipoproteins (HDL). Clinical studies have demonstrated an association between diminished PON-1 and the progression of chronic kidney disease (CKD). However, whether decreased PON-1 is mechanistically linked to renal injury is unknown. We tested the hypothesis that the absence of PON-1 is mechanistically linked to the progression of renal inflammation and injury in CKD. Experiments were performed on control Dahl salt-sensitive rats (SSMcwi, hereafter designated SS rats) and Pon1 knock-out rats (designated SS-Pon1em1Mcwi, hereafter designated SS-PON-1 KO rats) generated by injecting a CRISPR targeting the sequence into SSMcwi rat embryos. The resulting mutation is a 7 bp frameshift insertion in exon 4 of the PON-1 gene. First, to examine the renal protective role of PON-1 in settings of CKD, ten-week-old, age-matched male rats were maintained on a high-salt diet (8% NaCl) for up to 5 weeks to initiate the salt-sensitive hypertensive renal disease characteristic of this model. We found that SS-PON-1 KO rats demonstrated several hallmarks of increased renal injury vs. SS rats including increased renal fibrosis, sclerosis, and tubular injury. SS-PON-1 KO also demonstrated increased recruitment of immune cells in the renal interstitium, as well as increased expression of inflammatory genes compared to SS rats (all p < 0.05). SS-PON-1 KO rats also showed a significant (p < 0.05) decline in renal function and increased renal oxidative stress compared to SS rats, despite no differences in blood pressure between the two groups. These findings suggest a new role for PON-1 in regulating renal inflammation and fibrosis in the setting of chronic renal disease independent of blood pressure.

Biofilm modulatory response of arginine-fluoride varnish on multi-species biofilm.

OBJECTIVES: To examine the biofilm modulatory effect of arginine (Arg)-fluoride (F) varnish on multi-species biofilms. METHODS: Experimental varnishes were prepared by incorporating L-Arg (1, 2, and 4%) in 5% NaF varnish, which served as the control. Multi-species biofilms comprising Streptococcus mutans, Streptococcus sanguinis and Streptococcus gordonii were grown on hydroxyapatite (HA) discs and treated with the Arg and F released from the experimental and control groups. The HA discs with treated biofilms were examined for biofilm composition. The biofilm thickness and live/dead counts were investigated using confocal microscopic imaging, while biofilm polysaccharides, proteins, and extracellular DNA (eDNA) were assessed spectrophotometrically. Bacterial composition in biofilms was analysed using viability real-time quantitative polymerase chain reaction (qPCR). The relative gene expression (RGE) was determined for gtfB, SMU.150, nlmD, arcA, and sagP. RESULTS: Both the 2 and 4% Arg-NaF groups reduced biofilm thickness, with the 4% Arg-NaF group showing a significantly greater proportion of dead bacteria, followed by 1 and 2% Arg-NaF (p < 0.001). All Arg-NaF groups significantly reduced the carbohydrate content of the biofilm, while the 4% Arg-NaF-treated biofilms demonstrated higher concentration of eDNA and proteins compared to the control NaF (p < 0.001). Expression of gtfB, SMU.150, and nlmD were significantly downregulated in 4% Arg-NaF-treated biofilms; while 2% Arg-NaF enhanced the expression of arcA. Both 2% Arg-NaF and 4% Arg-NaF significantly increased the expression of sagP. CONCLUSION: The incorporation of L-arginine (2%/4%) enhances the biofilm modulatory effect of 5% NaF varnish through released Arg and F. CLINICAL SIGNIFICANCE: The study results indicate that Arg-F varnish (at 2%/4% w/v. Arg) has the potential to modulate cariogenic biofilms in high-risk individuals.

The acid-resistance potential of arginine-fluoride varnish treated enamel.

The study objective was to examine the acid-resistance potential of enamel carious lesions treated with arginine (Arg)-sodium fluoride (NaF) varnishes using nano-mechanical testing and chemical mapping. L-arginine (at 1%, 2%, & 4%) was incorporated in 5% NaF varnish. The experimental/control groups were: 1% Arg-NaF, 2% Arg-NaF, 4% Arg-NaF, NaF, and no treatment. Enamel specimen blocks were subjected to incipient carious lesion formation. After treatment, the specimens underwent chemical pH-cycling for 8-days and acid challenge for 2 h. The specimens were characterised for surface nano-hardness (SNH) and calcium/phosphate content of the treated lesions to determine enamel solubility reduction (ESR). Post-acid challenge, X-ray diffraction crystallography (XRD), and energy dispersive X-ray spectrophotometry (EDX) were performed. The SNH for 2%/4% Arg-NaF demonstrated a higher resistance to acid challenge with significantly higher SNH recovery than NaF varnish (p<0.05). The ESR potential of 2%/4% Arg-NaF varnish was significantly higher than NaF varnish (p<0.05). The XRD crystalline phases demonstrated that 2%/4% Arg-NaF had intense hydroxyapatite peaks discerning its increased potential to resist demineralization than NaF varnish. The EDX results showed that 2%/4% Arg-NaF demonstrated Ca/P ratio closer to hydroxyapatite (~1.67) post-acid challenge. Incorporating 2%/4% L-arginine in a 5% NaF varnish enhances the acid-resistance potential of NaF varnish.

The retromandibular transparotid approach vs. retromandibular retroparotid approach for the mandibular condyle: our clinical experience

Aim: The mandible is regarded as a frequently fractured bone in patients who present with maxillofacial trauma accounting for almost 15.5% to 59% of all facial fractures. Managing condylar trauma has remained to be a point of contention amongst experts, regardless of the advances in surgical modalities and methodologies, and the treatment plan is often determined by the preference and the experience of the surgeon. There exist various approaches in the literature, each with its own specific benefits and drawbacks. With this study, we aimed to evaluate the prevalence of post-operative complications in patients who experienced ORIF by means of the retromandibular approach, by comparing the outcomes of one group having undergone transparotid surgery, with another that underwent retroparotid surgery. Methods: An experimental trial was undertaken. Convenience sampling was done from among the cases of condylar neck and base fracture visiting the department of OMFS, Dow University of Health Sciences from January 2017 to December 2019. An overall 26 patients were divided into 2 groups of 13 members each; one was managed using Open Reduction Internal Fixation (ORIF) by means of a retromandibular transparotid approach while the other group was treated with ORIF by means of a retromandibular retroparotid approach. A 6 month follow-up was done to assess range of active motion, occlusion, and complications such as deviation/deflection, neural injury, infections, sialocele, salivary fistulae and Frey's syndrome in both groups. Results: There was no statistically significant difference between the two groups in terms of inter-incisal opening, right and left lateral movements, or protrusion. One patient in the retroparotid group had deviation on mouth opening (7.69%), while one in the transparotid group reported with infection (7.69%), and 2 developed post operative seromas (15.38%). None had persisting facial nerve palsy at 6 months. Conclusion: We find no significant disparity between the 2 approaches at a follow-up of 6 months; therefore, the primary determining factor for selection of either technique is surgeon preference and appropriate case selection

Epigenetic processes during preeclampsia and effects on fetal development and chronic health.

Preeclampsia (PE), the leading cause of maternal and fetal morbidity and mortality, is associated with poor fetal growth, intrauterine growth restriction (IUGR) and low birth weight (LBW). Offspring of women who had PE are at increased risk for cardiovascular (CV) disease later in life. However, the exact etiology of PE is unknown. Moreover, there are no effective interventions to treat PE or alleviate IUGR and the developmental origins of chronic disease in the offspring. The placenta is critical to fetal growth and development. Epigenetic regulatory processes such as histone modifications, microRNAs and DNA methylation play an important role in placental development including contributions to the regulation of trophoblast invasion and remodeling of the spiral arteries. Epigenetic processes that lead to changes in placental gene expression in PE mediate downstream effects that contribute to the development of placenta dysfunction, a critical mediator in the onset of PE, impaired fetal growth and IUGR. Therefore, this review will focus on epigenetic processes that contribute to the pathogenesis of PE and IUGR. Understanding the epigenetic mechanisms that contribute to normal placental development and the initiating events in PE may lead to novel therapeutic targets in PE that improve fetal growth and mitigate increased CV risk in the offspring.

Deep transcriptomic profiling of Dahl salt-sensitive rat kidneys with mutant form of Resp18.

Expression of Regulated endocrine specific protein 18 (Resp18) is localized in numerous tissues and cell types; however, its exact cellular function is unknown. We previously showed that targeted disruption of the Resp18 locus in the Dahl SS (SS) rat (Resp18mutant) results in higher blood pressure (BP), increased renal fibrosis, increased urinary protein excretion, and decreased mean survival time following a chronic (6 weeks) 2% high salt (HS) diet compared with the SS rat. Based on this prominent renal injury phenotype, we hypothesized that targeted disruption of Resp18 in the SS rat promotes an early onset hypertensive-signaling event through altered signatures of the renal transcriptome in response to HS. To test this hypothesis, both SS and Resp18mutant rats were exposed to a 7-day 2% HS diet and BP was recorded by radiotelemetry. After a 7-day exposure to the HS diet, systolic BP was significantly increased in the Resp18mutant rat compared with the SS rat throughout the circadian cycle. Therefore, we sought to investigate the renal transcriptomic response to HS in the Resp18mutant rat. Using RNA sequencing, Resp18mutant rats showed a differential expression of 25 renal genes, including upregulation of Ren. Upregulation of renal Ren and other differentially expressed genes were confirmed via qRT-PCR. Moreover, circulating renin activity was significantly higher in the Resp18mutant rat compared with the WT SS rat after 7 days on HS. Collectively, these observations demonstrate that disruption of the Resp18 gene in the SS rat is associated with an altered renal transcriptomics signature as an early response to salt load.

Validation of Second-Generation Motion-Correction Software for Computed Tomography Coronary Angiography With Novel Quantitative Approach.

INTRODUCTION: Computed tomography of the coronary arteries (CTCA) is an important diagnostic tool. However, motion degradation is sometimes a challenge to interpretation and quantification, particularly with elevated heart rates. Here, a novel quantitative method is presented as part of an evaluation of one particular motion correction algorithm. METHODS: Computed tomography of the coronary arteries scans from 49 patients, with heart rates of >70 bpm, were identified with motion artifacts in multiple coronary segments. At these foci (196), an objective measure of motion degradation, defined here by cross-section eccentricity, was determined before and after image processing with second-generation GE SnapShot Freeze software (SSF-2.0). In addition, a subjective scoring was applied by an expert cardiothoracic radiologist both before and after processing. RESULTS: An overall decrease in vessel eccentricity strongly correlated (P < 0.001) with processing of the images by motion-correction software. A concurrent overall increase in subjective vessel clarity correlated (P < 0.001) with application of the software as well. CONCLUSIONS: A novel quantitative method (and subjective analysis) for evaluation of CTCA motion has been described and applied to validation of SSF-2.0 motion-correction software. Both the technique and software demonstrate promise for robust clinical utility in CTCA evaluation.

The effect of arginine-fluoride varnish on biochemical composition of multi-species biofilm.

OBJECTIVE: To examine the biochemical components of multi-species biofilm on the arginine (Arg)-sodium fluoride (NaF) varnish-treated enamel following bacterial pH-cycling. METHODS: l-arginine (at 1%, 2%, & 4% w/v.) was incorporated in a 5% NaF varnish. The experimental and control groups were: 1%, 2%, 4% Arg-NaF, NaF, and no treatment. Enamel blocks were prepared, acid-etched, varnish-treated and then subjected to 72 h bacterial pH-cycling in an oral biofilm reactor. The organic (carbohydrates, proteins, amyloids, and eDNA) and inorganic components (calcium, inorganic phosphate, F) were assayed for the obtained biofilm suspensions. The biofilms were stained for exopolysaccharides (EPS)/bacteria and the respective proportions of live/dead bacteria was determined using confocal imaging. RESULTS: The total carbohydrate content of the biofilm was the lowest for the 2% and 4% Arg-NaF (p < 0.05). Except for 2% Arg-NaF, the biofilm proteins for 4% Arg-NaF were significantly higher than the other groups (p < 0.05). The amyloids for Arg-NaF groups were significantly lower than the controls (p < 0.05). The eDNA for 4% Arg-NaF was significantly higher than the controls (p < 0.05). The 2% and 4% Arg-NaF-treated enamel had increased biofilm Pi and F compared to the NaF-treated enamel (p < 0.05). The proportion of biofilm EPS matrix to bacteria was significantly reduced in Arg-NaF groups compared to the controls (p < 0.05). The dead bacterial proportions of 4% Arg-NaF were significantly higher than the controls (p < 0.05). CONCLUSION: Higher concentrations (i.e. 2%/4%) of Arg in 5% NaF varnish have the potential to modulate the biochemical composition of the biofilm growing on the treated enamel.

Physiological Oxygen Tension Enhances Competence and Functional Properties of Murine Cardiac Mesenchymal Cells.

Cardiac mesenchymal cells (CMCs), a newly-discovered and promising type of progenitor cells, are effective in improving cardiac function in rodents after myocardial infarction. Stem/progenitor cells are usually cultured at atmospheric O2 tension (21%); however, the physiologic O2 tension in the heart is ~5%, raising the concern that 21% O2 may cause toxicity due to oxidative stress. Thus, we compared mouse CMCs cultured at 21% or 5% O2 beginning at passage 2. At passage 5, CMCs underwent severe hypoxic stress (1% O2 for 24 h). Compared with CMCs cultured at 21% O2, culture at 5% O2 consistently improved cell morphology throughout 5 passages, markedly decreased cell size, increased cell number, shortened cell doubling time, and dramatically reduced lactate dehydrogenase release from CMCs into culture media after hypoxic stress. Furthermore, culture at 5% O2 increased telomerase activity and telomere length, implying that 21% O2 tension impairs telomerase activity, resulting in telomere shortening and decreased cell proliferation. Thus far, almost all preclinical and clinical studies of cell therapy for the heart disease have used atmospheric (21%) O2 to culture cells. Our data challenge this paradigm. Our results demonstrate that, compared with 21% O2, 5% O2 tension greatly enhances the competence and functional properties of CMCs. The increased proliferation rate at 5% O2 means that target numbers of CMCs can be achieved with much less time and cost. Furthermore, since this increased proliferation may continue in vivo after CMC transplantation, and since cells grown at 5% O2 are markedly resistant to severe hypoxic stress, and thus may be better able to survive after transplantation into scarred regions of the heart where O2 is very low, culture at 5% O2 may enhance the reparative properties of CMCs (and possibly other cell types). In conclusion, our data support a change in the methods used to culture CMCs and possibly other progenitor cells.

SARS-CoV-2, ACE2 expression, and systemic organ invasion.

A novel coronavirus disease, COVID-19, has created a global pandemic in 2020, posing an enormous challenge to healthcare systems and affected communities. COVID-19 is caused by severe acute respiratory syndrome (SARS)-coronavirus-2 (CoV-2) that manifests as bronchitis, pneumonia, or a severe respiratory illness. SARS-CoV-2 infects human cells via binding a "spike" protein on its surface to angiotensin-converting enzyme 2 (ACE2) within the host. ACE2 is crucial for maintaining tissue homeostasis and negatively regulates the renin-angiotensin-aldosterone system (RAAS) in humans. The RAAS is paramount for normal function in multiple organ systems including the lungs, heart, kidney, and vasculature. Given that SARS-CoV-2 internalizes via ACE2, the resultant disruption in ACE2 expression can lead to altered tissue function and exacerbate chronic diseases. The widespread distribution and expression of ACE2 across multiple organs is critical to our understanding of the varied clinical outcomes of COVID-19. This perspective review based on the current literature was prompted to show how disruption of ACE2 by SARS-CoV-2 can affect different organ systems.

Enamel remineralization potential of arginine-fluoride varnish in a multi-species bacterial pH-cycling model.

OBJECTIVES: To examine the enamel fluoride uptake and remineralization potential of arginine-fluoride (Arg-NaF) varnishes in a simulated clinical condition using a multi-species bacterial pH-cycling model. METHODS: L-Arginine (at 1 %, 2 %, and 4 % by wt.) was incorporated in a 5 % NaF varnish. Experimental and control groups were: 1 % Arg-NaF; 2 % Arg-NaF; 4 % Arg-NaF; NaF and no treatment. Artificial incipient caries-like lesions were formed on 30 enamel specimen blocks (n = 6). The specimens underwent multi-species bacterial pH-cycling in an artificial mouth system using oral biofilm reactor for 72 h after treatment. The specimens were evaluated for mineral density using micro-CT, Ca/P ratio with SEM-EDX, enamel fluoride uptake (EFU) and plaque fluoride uptake (PFU). RESULTS: Increasing concentrations of Arg in NaF varnish significantly increased the EFU of incipient caries-like lesions (p < 0.001). The PFU for 1 % Arg-NaF was significantly higher than 4 % Arg-NaF and the control NaF (p < 0.05). Post pH-cycling, Ca/P ratio with 1 %/2 % Arg-NaF was closest to hydroxyapatite (1.67). Mineral gain and % remineralization of 1 %/2 % Arg-NaF was significantly higher than the control NaF varnish (p < 0.05). CONCLUSION: The prebiotic L-arginine (at 1 %/2 % by wt.) in a 5 % NaF varnish enhanced the enamel fluoride uptake and remineralization potential of the conventional 5 % NaF varnish. CLINICAL SIGNIFICANCE: The Arg-NaF varnish addresses the limitations of fluorides on cariogenic biofilms. The Arg-NaF varnish appears a promising caries-preventive regimen that counters the pathogenic biofilms by Arg and promotes remineralization with fluorides. In high caries-risk patients, professional application of Arg-NaF varnish might aid to alleviate the global burden of dental caries.

Pattern Matching for DNA Sequencing Data Using Multiple Bloom Filters.

Storing and processing of large DNA sequences has always been a major problem due to increasing volume of DNA sequence data. However, a number of solutions have been proposed but they require significant computation and memory. Therefore, an efficient storage and pattern matching solution is required for DNA sequencing data. Bloom filters (BFs) represent an efficient data structure, which is mostly used in the domain of bioinformatics for classification of DNA sequences. In this paper, we explore more dimensions where BFs can be used other than classification. A proposed solution is based on Multiple Bloom Filters (MBFs) that finds all the locations and number of repetitions of the specified pattern inside a DNA sequence. Both of these factors are extremely important in determining the type and intensity of any disease. This paper serves as a first effort towards optimizing the search for location and frequency of substrings in DNA sequences using MBFs. We expect that further optimizations in the proposed solution can bring remarkable results as this paper presents a proof of concept implementation for a given set of data using proposed MBFs technique. Performance evaluation shows improved accuracy and time efficiency of the proposed approach.

SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs.

The present study describes the synthesis of a series of 22 chalcone analogs. These compounds were evaluated as potential human MAO-A and MAO-B inhibitors. The compounds showed varied selectivity against the two isoforms. The IC50 values were found to be in the micromolar to submicromolar range. The Ki values of compound 16 were determined to be 0.047 and 0.020 µM for the inhibition of MAO-A and MAO-B, respectively. Dialysis of enzyme-inhibitor mixtures indicated a reversible competitive mode of inhibition. Most of the synthesized chalcone analogs showed a better selectivity toward MAO-B. However, introducing of 2,4,6-trimethoxy substituents on ring B shifted the selectivity toward MAO-A. In addition, we investigated the molecular mechanism of MAO-B inhibition by selected chalcone analogs. Our results revealed that these selected chalcone analogs increased dopamine levels in the rat hepatoma (H4IIE) cells and decreased the relative mRNA expression of the MAO-B enzyme.

COUP-TFII revisited: Its role in metabolic gene regulation.

Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) is an orphan member of the nuclear receptor family of transcriptional regulators. Although hormonal activation of COUP-TFII has not yet been identified, rodent genetic models have uncovered vital and diverse roles for COUP-TFII in biological processes. These include control of cardiac function and angiogenesis, reproduction, neuronal development, cell fate and organogenesis. Recently, an emerging body of evidence has demonstrated COUP-TFII involvement in various metabolic systems such as adipogenesis, lipid metabolism, hepatic gluconeogenesis, insulin secretion, and regulation of blood pressure. The potential relevance of these observations to human pathology has been corroborated by the identification of single nucleotide polymorphism in the human COUP-TFII promoter controlling insulin sensitivity. Of particular interest to metabolism is the ability of COUP-TFII to interact with the Glucocorticoid Receptor (GR). This interaction is known to control gluconeogenesis, principally through direct binding of COUP-TFII/GR complexes to the promoters of gluconeogenic enzyme genes. However, it is likely that this interaction is critical to other metabolic processes, since GR, like COUP-TFII, is an essential regulator of adipogenesis, insulin sensitivity, and blood pressure. This review will highlight these unique roles of COUP-TFII in metabolic gene regulation.