Instability and translocation through nanopores of DNA interacting with single-layer materials

In this study, we use classical applied mathematical modelling to employ the 6–12 Lennard-Jones potential function along with the continuous approximation to investigate the interaction energies between a double-stranded deoxyribonucleic acid (dsDNA) molecule and two-dimensional nanomaterials, namely graphene (GRA), hexagonal boron nitride (h-BN), molybdenum disulphide (MoS₂), and tungsten disulphide (WS₂). Assuming that the dsDNA molecule has a perpendicular distance Δ above the nano-sheet surface, we calculated the molecular interaction energy and determined the relation between the location of the minimum energy and Δ. We also investigated the interaction of a dsDNA molecule with the surface of each nano-sheet in the presence of a circular hole simulating a nanopore. The radius of the nanopore that results in the minimum energy was determined. Our results show that the adsorption energies of the dsDNA molecule with GRA, h-BN, MoS₂, and WS₂ nano-sheets corresponding to the perpendicular distance Δ = 20 Å are approximately 70, 82, 28, and 26 (kcal mol⁻¹), respectively, and we observed that the dsDNA molecule moves through nanopores of radii greater than 12.2 Å.

Using classical applied mathematical modelling to employ the 6–12 Lennard-Jones potential function along with the continuous approximation to investigate the interaction energy between dsDNA and 2D-nanomaterials, namely GRA, h-BN, MoS₂ and WS₂ sheets.     

Study of Surgical Emergencies of Tubercular Abdomen in Developing Countries

To study the various modes of presentation, diagnosis, and management of surgical emergencies of tubercular abdomen. This prospective study of surgical emergencies of tubercular abdomen was conducted in 50 patients who attended our surgical emergency from 2006 to 2008. Patients were evaluated thoroughly with history, physical examination, routine investigations, and special investigations such as ELISA, PCR, barium studies of gastrointestinal tract, and diagnostic laparoscopy as required and managed with medical and surgical treatment as necessary. The most of patients were from rural areas, in the third to sixth decades with slight male preponderance. Abdominal pain, vomiting, and constipation were commonest presenting symptoms. About 20 % patients had history of pulmonary tuberculosis and 16 % patients presented with ascites. PCR for blood and ascitic fluid was positive in 72 and 87.5 % patients, respectively. About 24 % patients were managed nonoperatively and responded to ATT. About 76 % patients needed surgery among which one-fifth of patients were operated in emergency. Procedures like adhesiolysis of gut (47.3 %), strictureplasty (10.5 %), resection anastomosis (5.2 %), right hemicolectomy (5.2 %), and ileotransverse anastomosis (7.8 %) were performed in 30 patients and peritoneal biopsy and lymph node biopsy in the remaining 8 patients. Both medically and surgically managed patients were put on antitubercular therapy. Abdominal tuberculosis is a disease of middle-aged rural people, presenting commonly with abdominal pain and vomiting with right lower abdominal tenderness. PCR (blood and ascites) for tuberculosis is much more sensitive than IgM ELISA (blood and ascites). The most of patients required surgical procedures and all patients responded dramatically to antitubercular therapy symptomatically with increase in the hemoglobin level and decrease in ESR.     

The Premonitory Phase of Migraine – What Can We Learn From It?

This review aims to understand the prevalence of premonitory symptoms in migraine, postulate their mechanisms, and compare these with functional imaging studies. A thorough literature review was conducted using PubMed for prevalence studies of premonitory symptoms in migraine and functional imaging studies in the premonitory phase. The majority of studies have been retrospective reporting a prevalence of 7‐88% for premonitory symptoms in migraine. Only one study has investigated premonitory symptoms prospectively and used preselected patients with recognized premonitory symptoms. The majority of patients were able to predict correctly the onset of migraine headache. Only one functional imaging study has been conducted in the premonitory phase that showed activation of posterolateral hypothalamus, midbrain tegmental area and substantia nigra, periaqueductal gray, dorsal pons, and various cortical areas including occipital, temporal, and prefrontal cortex. Subgroup analysis of patients with photophobia more than without photophobia in the premonitory phase showed activation of the occipital cortex. Comparison of patients with nausea more than without nausea in the premonitory phase showed activation in upper dorsal medulla and periaqueductal gray. Premonitory symptoms are common in migraine, although the true prevalence cannot be stated with certainty in the absence of prospective studies in unselected patients. Hypothalamic involvement can explain many of the premonitory symptoms. Activation of the the brainstem structures and hypothalamus before pain suggests a pivotal role of these structures in the pathogenesis of migraine. Hypersensitivity to light and occurrence of nausea in migraine is associated with activation of central brain structures involved in these pathways, and this can occur in the absence of pain.     

Thioredoxin-Interacting Protein Deficiency Protects against Diabetic Nephropathy

Expression of thioredoxin-interacting protein (TxNIP), an endogenous inhibitor of the thiol oxidoreductase thioredoxin, is augmented by high glucose (HG) and promotes oxidative stress. We previously reported that TxNIP-deficient mesangial cells showed protection from HG-induced reactive oxygen species, mitogen-activated protein kinase phosphorylation, and collagen expression. Here, we investigated the potential role of TxNIP in the pathogenesis of diabetic nephropathy (DN) in vivo. Wild-type (WT) control, TxNIP^−/−, and TxNIP^+/− mice were rendered equally diabetic with low-dose streptozotocin. In contrast to effects in WT mice, diabetes did not increase albuminuria, proteinuria, serum cystatin C, or serum creatinine levels in TxNIP^−/− mice. Whereas morphometric studies of kidneys revealed a thickened glomerular basement membrane and effaced podocytes in the diabetic WT mice, these changes were absent in the diabetic TxNIP^−/− mice. Immunohistochemical analysis revealed significant increases in the levels of glomerular TGF-β1, collagen IV, and fibrosis only in WT diabetic mice. Additionally, only WT diabetic mice showed significant increases in oxidative stress (nitrotyrosine, urinary 8-hydroxy-2-deoxy-guanosine) and inflammation (IL-1β mRNA, F4/80 immunohistochemistry). Expression levels of Nox4-encoded mRNA and protein increased only in the diabetic WT animals. A significant loss of podocytes, assessed by Wilms’ tumor 1 and nephrin staining and urinary nephrin concentration, was found in diabetic WT but not TxNIP^−/− mice. Furthermore, in cultured human podocytes exposed to HG, TxNIP knockdown with siRNA abolished the increased mitochondrial O₂⁻ generation and apoptosis. These data indicate that TxNIP has a critical role in the progression of DN and may be a promising therapeutic target.     

Prevalence of dental caries in primary and permanent teeth and its relation with tooth brushing habits among schoolchildren in Eastern Saudi Arabia

Objectives:

To determine the prevalence of dental caries in the primary and permanent teeth, and evaluate the brushing habits of school children in Dammam, Kingdom of Saudi Arabia (KSA).

Methods:

This study was conducted at Dammam, KSA. Oral examination of the participants was conducted from February to May 2014. The total sample size for this cross-sectional study was 711. There were 397 children between the age of 6-9 years, who were examined for primary teeth caries, and 314 between the age 10-12 years were examined for permanent teeth caries. Primary and permanent dentitions were studied for decayed, missing, and filled teeth (dmft [primary teeth], DMFT [permanent teeth]).

Results:

The overall prevalence of dental caries in primary and permanent teeth was almost 73% (n=711). Among the 6-9-year-old, the prevalence of caries was approximately 78% (n=397) whereas, among the 10-12-year-old children, it was approximately 68% (n=314). Mean dmft value among the 6-9-year-olds was 3.66±3.13 with decayed (d) component of 3.28±2.92, missing (m) component of 0.11±0.69, and filled (f) component of 0.26±0.9. Mean DMFT value among the 10-12-year-old children was 1.94±2.0 with decayed (D) component of 1.76±1.85, missing (M) component of 0.03±0.22, and filled (F) of component 0.15±0.73. Daily tooth brushing had a positive effect on caries prevention, and this effect was statistically significant for caries in primary teeth.

Conclusion:

Although the prevalence of dental caries in primary and permanent teeth was not found to be as high as other researchers reported from different cities of KSA, still the prevalence was high considering the World Health Organization future oral health goals. Awareness should be provided to students, as well as, teachers and parents regarding the importance of good brushing habits and regular dental visits.Dental caries is one of the most common cause of extraction of primary teeth in Saudi Arabia.1 In the past few decades, an increase in the prevalence of dental caries has been observed, which can be attributed to a change in lifestyle of Saudis, involving increased consumption of sugary food, carbonated drinks, and lack of awareness towards proper oral health maintenance.2,3 Generally, the prevalence of dental caries in developed countries is decreasing, while in underdeveloped and developing countries, the prevalence is on the rise.4 According to the statistics available from the World Health Organization (WHO), caries prevalence among the 12-year-old children from many European Union states (EU) has decreased considerably from 1970’s to 2006.5 This decline in the caries’ prevalence among EU countries over a period of 35 years could be attributed to an increased awareness of oral hygiene maintenance, and use of fluoridated toothpaste.6 However, among underdeveloped countries where fluoridated toothpaste is not easily available, or not affordable in some cases, caries prevalence is still high.7 The area of dental caries prevalence is of great interest to local and international researchers, which can be indicated by a number of studies that have been performed in developed and developing countries regarding caries’ prevalence.8-10 A study conducted in the urban and rural areas of Lahore, Pakistan to determine whether urbanization and family earnings are related to dental caries reported caries prevalence of 40.5%, and decayed (d), missing (m), and filled (f) teeth (dmft [primary teeth]) score of 1.85 ± 3.26 in preschool children aged 3-5 years,11 while another cross-sectional study performed in Chikar, Pakistan with convenience sampling of 311 schoolchildren revealed an overall DMFT (permanent teeth) score of 3.3 in 5-20-year-olds.12 Several studies have been conducted in different parts of the Kingdom of Saudi Arabia (KSA) to report the prevalence of dental caries in schoolchildren. A study performed in Riyadh reported a dmft score of 6.1, decayed factor of 4.6, and no significant difference in the prevalence of caries in relation to gender among 789 pre-school children.13 Farsi14 conducted a study to develop an association between enamel defects and caries occurrence in Jeddah, KSA, and reported a dmft score of 3.9, and a strong association between enamel defects and caries prevalence among 4-5-year-olds.14 In 2012, caries prevalence in the maxillary and mandibular first molar in the age group of 7-10 years schoolchildren was determined in Abha city, and a mean DMFT of 2.74 was reported.15 It was also concluded in the same study that caries prevalence in the first permanent molars from this region is higher than the recommended standards of the WHO.15 Extensive literature search was carried out to find studies regarding caries’ prevalence from Dammam, KSA. The search resulted in only one study, which was conducted in 2008 on children with cleft lip and palate aged 1-6 years, and it reported a high dmft of 10.54 from Dammam region.16 Since Dammam is one of the largest cities of the Eastern province of KSA, it would be interesting to observe caries’ prevalence among schoolchildren from this city. Therefore, the aim of the present study was to determine the prevalence of dental caries in schoolchildren aged 6-12 years in Dammam, KSA using the dmft/DMFT index of dental caries.     

Reversible regional wall motion abnormalities on exercise technetium-99m-gated cardiac single photon emission computed tomography predict high-grade angiographic stenoses

OBJECTIVES: We sought to determine the level of angiographic stenosis at which reversible regional wall motion abnormalities (RWMA) are present on exercise stress technetium-99m (Tc-99m)- gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and whether assessments of stress and rest RWMA add incremental diagnostic information. BACKGROUND: Stress and rest gated SPECT MPI enables the detection of post-exercise stunning. Although some studies have correlated RWMA to the severity of MPI defects, only one previous study correlated RWMA on gated MPI to angiographic findings. However, this correlation excluded patients with rest perfusion defects and did not involve gating of rest images. METHODS: One hundred patients undergoing angiography within six months of exercise stress Tc-99m (sestamibi)-gated SPECT MPI (in the absence of interim cardiac events or revascularization) were recruited. Images were acquired 15 to 30 min after stress and interpreted without knowledge of the Duke treadmill score, left ventricular ejection fraction and angiographic data. RESULTS: The sensitivity of reversible RWMA for angiographic stenoses >70% was 53%, with a specificity of 100%. The presence of reversible RWMA was able to stratify patients with angiographic stenoses of 50% to 79% and 80% to 99% with a high positive predictive value. A good correlation was noted between the presence of reversible RWMA and the coronary artery jeopardy score (R = 0.49, p < 0.0001). Multivariate analysis showed that the post-stress RWMA, Duke treadmill and reversible RWMA scores were significant predictors of angiographic severity. CONCLUSIONS: Post-stress and reversible RWMA, as shown by exercise stress Tc-99m-gated SPECT MPI, are significant predictors of angiographic disease and add incremental value to MPI for the assessment of angiographic severity.     

Measuring Adherence by Visual Inspection of Returned Empty Gel Applicators in the CAPRISA 004 Microbicide Trial

In the CAPRISA 004 trial, adherence was estimated as the proportion of reported sex acts covered by two gel doses, which was assessed by counting returned empty gel applicators. The returned empty applicators were inspected visually in a standardized manner for residue on the outside of the applicator, as an indicator of vaginal insertion. Over 15 months, spanning 11,839 study visits by 838 women, a total of 59,800 returned empty applicators were inspected. By visual assessment, 77.5 % of these applicators appeared to have been inserted. To test the accuracy of the assessment we fitted a Cox model and found that the risk for HIV infection was doubled when less than half of the returned empty applicators had been assessed as not inserted in the vagina. Visual inspection enhanced both the accuracy of the adherence measurement and aided identification of mechanical problems with applicator use experienced by women in the trial.     

Disclosure of Microbicide Gel Use to Sexual Partners: Influence on Adherence in the CAPRISA 004 Trial

Young women in sub-Saharan Africa are disproportionately affected by HIV, making the development of women initiated and controlled methods of prevention, including microbicides, a priority. Adherence is pivotal to microbicide efficacy and partner related factors are known to impact adherence. An analysis of disclosure of gel use to sexual partners and adherence in CAPRISA 004 women was conducted to better understand this relationship. Partner disclosure was significantly associated with a modest 4.2 % increased adherence (71.0 vs. 66.8 %, p = 0.03). Most women rated the experience of disclosure as positive, despite 6.7 % of partners expressing a negative reaction.Participants who disclosed were more likely to reside with their regular partner (14.4 vs. 8.4 %; p = 0.01) and reported consistent condom use at baseline (32.9 vs. 20.9 %; p < 0.01). Partner disclosure needs to be better understood as a potential facilitator or barrier to microbicide adherence.