Miracle-dz/UniFAR-FTUs huggingface dataset:
The use of E-test for the drug susceptibility testing of Mycobacterium tuberculosis - a solution or an illusion?

AIM To evaluate E-test as a tool for rapid determination of drug susceptibility against the conventional LJ method focusing on reliability, expense, ease of standardization and performance of the technique in low resource settings. MATERIALS AND METHODS A total of 74 clinical isolates (2004-2005) of Mycobacterium tuberculosis were tested using E-test for susceptibility to streptomycin (STM), isoniazid (INH), rifampicin (RIF) and ethambutol (EMB) by E-strip and LJ (LJPM) proportion methods. RESULTS The LJPM method, the gold standard, detected resistance against STM in 16.2%, INH in 40.5%, RIF in 18.9% and EMB in 27% cases. In comparison, the resistance values showed by E-test was 66.67% for STM, 57.14% for INH 71.43% for RIF and 80% for EMB. The susceptible correlation was 90.32% for STM, 73.91% for INH, 93.33% for RIF and 59.26% for EMB. E-test correctly identified only eight of the 12 (66.6%) MDR isolates and wrongly identified four isolates which were not MDR. The overall agreement between the two methods was only 48.6%. Resistant isolates showed false positive resistance observed while using E-strip towards all the drugs. CONCLUSION E-strips are not quite feasible as a replacement for LJ-proportion method on a large scale due to high risk of cross contamination, laboratory infection, expense associated with it and high false positive resistance observed to all first line drugs. However, the good correlation observed for RIF between the two methods indicates that E-test could contribute to the role in rapid screening of MDR TB isolates as rifampicin mutations are invariably observed in MDR TB isolates.
Tailored Health Communication to Change Lifestyle Behaviors

Tailored health communication research represents a very promising line of inquiry that has the potential to produce major impacts on lifestyle behaviors. This study defines tailoring and discusses how tailored interventions operate, including comparing/ contrasting different tailoring channels. Next, the authors review the literature on tailored interventions to change lifestyle behaviors, with a focus on smoking cessation, dietary change, and physical activity, as well as interventions that address multiple lifestyle behaviors. Finally, future directions for tailoring research are discussed. To date, a large literature has amassed showing the promise of tailored programs delivered via print, Internet, local computer/kiosk, telephone, and interpersonal channels. Numerous studies demonstrate that these programs are capable of significant impacts on smoking cessation, dietary change, physical activity, and multiple behavior change. It is concluded that the potential of tailoring will be more fully realized as (a) the field builds a more cumulative science of tailoring and (b) greater dissemination of efficacious tailored programs takes place.
Imaging and Quantification of Endothelial Cell Loss in Eye Bank Prepared DMEK Grafts Using Trainable Segmentation Software

Abstract Purpose: To improve accuracy and efficiency in quantifying the endothelial cell loss (ECL) in eye bank preparation of corneal endothelial grafts. Methods: Eight cadaveric corneas were subjected to Descemet Membrane Endothelial Keratoplasty (DMEK) preparation. The endothelial surfaces were stained with a viability stain, calcein AM dye (CAM) and then captured by a digital camera. The ECL rates were quantified in these images by three separate readers using trainable segmentation, a plug-in feature from the imaging software, Fiji. Images were also analyzed by Adobe Photoshop for comparison. Mean times required to process the images were measured between the two modalities. Results: The mean ECL (with standard deviation) as analyzed by Fiji was 22.5% (6.5%) and Adobe was 18.7% (7.0%; p = 0.04). The mean time required to process the images through the two different imaging methods was 19.9 min (7.5) for Fiji and 23.4 min (12.9) for Adobe (p = 0.17). Conclusions: Establishing an accurate, efficient and reproducible means of quantifying ECL in graft preparation and surgical techniques can provide insight to the safety, long-term potential of the graft tissues as well as provide a quality control measure for eye banks and surgeons. Trainable segmentation in Fiji software using CAM is a novel approach to measuring ECL that captured a statistically significantly higher percentage of ECL comparable to Adobe and was more accurate in standardized testing. Interestingly, ECL as determined using both methods in eye bank-prepared DMEK grafts exceeded 18% on average.
Meibomian Gland Dropout in Patients with Dry Eye Disease in China

Abstract Purpose: To examine the morphological changes in the meibomian glands of eyes of patients with dry eye disease using the non-contact infrared meibography system and to assess their relationship with meibomian dropout, signs, and tear-film function. Methods: Subjects included 264 randomly selected patients (528 eyes) suffering from dry eye disease (95 males, 169 females; age range, 7–85 years; mean male age, 39.83 ± 19.17 years; mean female age, 46.16 ± 17.38 years). Tear-film break-up time (BUT) was measured and tear-film production was evaluated by the Schirmer test I (SIT). Subjective symptoms were also scored. The upper and lower eyelids were turned over, and the meibomian glands were observed using the non-contact meibography system. Partial or complete loss of the meibomian glands (meibomian dropout) was scored for each eyelid from grade 0 (no loss) through grade 3 (lost area was >2/3 of the total meibomian gland area). Results: The average SIT result was 6.71 ± 6.13 mm (range 0–30 mm) and that for BUT was 3.13 ± 2.39 s (range 0–10 s). The average fluorescein staining score was 4.25 ± 4.05 (range 0–12). In addition, the mean meibomian gland photographic score was 4.35 ± 1.39. The correlation between the meibomian gland photographic scores and various ocular surface examinations were evaluated using Kendall’s correlation. SIT and BUT were significantly negatively correlated with the meibomian gland photographic score, whereas corneal fluorescein staining was positively correlated. Conclusions: The results suggest a large proportion of meibomian dropout cases among patients with dry eye disease, indicating that treatment targeted at the meibomian gland will become an important direction for treating dry eye disease. Meibography is recommended as a routine test for dry eye disease.
Nested polymerase chain reaction on blood clots for gene encoding 56 kDa antigen and serology for the diagnosis of scrub typhus.

PURPOSE Scrub typhus is a zoonotic illness endemic in the Asia-Pacific region. Early diagnosis and appropriate management contribute significantly to preventing adverse outcomes including mortality. Serology is widely used for diagnosing scrub typhus. Recent reports suggest that polymerase chain reaction (PCR) could be a rapid and reliable alternative. This study assessed the utility of these tests for scrub typhus diagnosis. MATERIALS AND METHODS Nested PCR to detect the 56 kDa antigen gene of O. tsutsugamushi was performed on blood clots from 87 individuals with clinically suspected scrub typhus. Weil-Felix test and scrub typhus IgM ELISA were performed on serum samples from the same patients. As a gold standard reference test was not available, latent class analysis (LCA) was used to assess the performance of the three tests. RESULTS The LCA analysis showed the sensitivity of Weil-Felix test, IgM ELISA and PCR to be 59%, 100% and 58% respectively. The specificity of ELISA was only 73%, whereas those of the Weil-Felix test and PCR were 94% and 100% respectively. CONCLUSION Nested PCR using blood clots while specific, lacked sensitivity as compared to IgM ELISA. In resource-poor settings Weil-Felix test still remains valuable despite its moderate sensitivity.
Animal Models of Diabetic Retinopathy

Abstract Diabetic retinopathy (DR) is one of today’s main causes of blindness in numerous developed countries worldwide. The underlying pathogenesis of DR is complex and not well understood, thus impeding development of specific, effective treatment modalities. Consequently, the use of animal models of DR is of critical importance for investigating the pathogenesis of and treatment for DR. While rats and mice are the most commonly used animal models of DR, the zebrafish now appears to be a promising model. Nonhuman primates and humans have similar eye structures, and both can develop spontaneous diabetes mellitus (DM). Although various traditionally used animal models of DR undergo a number of pathological changes similar to those of human DR, several human variations, e.g. retinal neovascularization, cannot yet be fully mimicked in any existing animal model of DM. Since both the animal models and the methods chosen for inducing DR have great influence on experimental results, a clear understanding of available animal models is vital for planning an experimental design. In this review, we summarize the mechanisms, methodologies and pros and cons of the most commonly used animal models of DR.
A rapid and reliable species-specific identification of clinical and environmental isolates of Vibrio cholerae using a three-test procedure and recA polymerase chain reaction.

PURPOSE Vibrio cholerae, the cause of cholera, is one of the leading causes of morbidity and mortality in many developing countries. Most laboratories initially rely on biochemical tests for a presumptive identification of these strains, followed by a polymerase chain reaction (PCR)-based method to confirm their identification. The aim of this study is to establish a rapid and reliable identification scheme for V. cholerae using a minimal, but highly specific number of biochemical tests and a PCR assay. MATERIALS AND METHODS We developed a species-specific PCR to identify V. cholerae, using a housekeeping gene recA, and used that to evaluate the sensitivity and specificity of 12 biochemical tests commonly used for screening and / or presumptive identification of V. cholerae in the clinical and environmental samples. RESULTS Here we introduced a combination of three biochemical tests, namely, sucrose fermentation, oxidase test, and growth in trypton broth containing 0% NaCl, as also the PCR of the recA gene, for rapid identification of V. cholerae isolates, with 100% sensitivity and specificity. The established method accurately identified a collection of 47 V. cholerae strains isolated from the clinical cases (n = 26) and surface waters (n = 21), while none of the 32 control strains belonging to different species were positive in this assay. CONCLUSION The triple-test procedure introduced here is a simple and useful assay which can be adopted in cholera surveillance programs for efficient monitoring of V. cholerae in surface water and fecal samples.
Utility of GenoType MTBDRplus assay in rapid diagnosis of multidrug resistant tuberculosis at a tertiary care centre in India.

PURPOSE Molecular methods which allow rapid detection of tuberculosis as well as drug resistance directly from clinical samples have become the most popular diagnostic methodology with the emergence of multidrug resistant tuberculosis. The aim of the present study was to evaluate the performance of a line probe assay, GenoType MTBDRplus for the rapid detection of Mycobacterium tuberculosis and mutations causing rifampicin and INH resistance directly in smear positive pulmonary specimens and also in M. tuberculosis isolates grown from various clinical specimens. MATERIALS AND METHODS The MTBDRplus assay was done directly on 37 smear positive pulmonary specimens and also on 69 M. tuberculosis isolates obtained by rapid automated culture using Bact/Alert 3D. The results were compared with phenotypic drug susceptibility testing (1% proportion method) using Bact/Alert 3D. RESULTS The sensitivity and specificity for detection of resistance to rifampicin was 100% and 97.3%, and to INH was 91.9% and 98.4%, respectively, in comparison with the phenotypic drug susceptibility testing. CONCLUSION MTBDRplus assay had good sensitivity and specificity with turn around time of less than 48 hours. It may be a useful tool for rapid detection of multidrug resistant tuberculosis at a tertiary care centre.
Transsclera Drug Delivery by Pulsed High-Intensity Focused Ultrasound (HIFU): An Ex Vivo Study

Abstract Purpose/aim of study: Drug delivery to the ocular posterior segment is of importance, but it is a challenge in the treatment of irreversible blindness disease, such as age-related macular degeneration. Although some methods (i.e. intraocular injection, sustained release by polymer and iontophoresis) have been applied, some technical drawbacks, such as slow rate and damage to the eye, need to be overcome for wide use. Materials and methods: In this study, the feasibility of high-intensity focused ultrasound (HIFU) to enhance the transsclera drug delivery was tested for the first time. One-hundred HIFU pulses with the driving frequency of 1.1 MHz, acoustic power of 105.6 W, pulse duration of 10–50 ms and pulse repetition frequency of 1 Hz were delivered to the fresh ex vivo porcine sclera specimen. Results: In comparison to the passive diffusion (control), 50-ms HIFU can increase the penetration depth by 2.0 folds (501.7 ± 126.4 µm versus 252.4 ± 29.2 µm) using bicinchoninic acid assay and Rhodamine 6 G fluorescence intensity by 3.1 folds (22.4 ± 12.3 versus 7.1 ± 4.1) and coverage area by 2.6 folds (40.4 ± 9.1% versus 15.8 ± 2.9%). No morphological changes on the sonicated sclera samples were found using a surface electron microscope. Conclusions: In summary, pulsed-HIFU may be an effective modality in the transsclera drug delivery with a high transporting rate and depth. In vivo studies are necessary to further evaluate its performance, including the drug penetration and its possible side effects.
Rosmarinic Acid Suppresses Subconjunctival Neovascularization in Experimental Glaucoma Surgery

Abstract Purpose: Excessive subconjunctival scarring is associated with increased angiogenesis and leads to filtration failure in glaucoma surgery. In this study, we describe that rosmarinic acid (RA) has anti-angiogenic activity during wound healing in a rabbit model of glaucoma surgery. Methods: Forty New Zealand rabbits underwent an experimental trabeculectomy and were randomly allocated into two treatment groups: RA group – treated with subconjunctival injections of 0.1 ml RA (15 mg/ml; n = 20) – and control group – treated with subconjunctival injections of 0.1 ml balanced salt solution (n = 20). The in vivo effect of RA was investigated after 5 and 15 d by measuring the intraocular pressure (IOP; with Tonopen) and bleb area and vascularity (using the Moorfields Bleb Grading System). Vascularization was also studied by counting histological blood vessels and by immunohistochemistry of vascular endothelial growth factor (VEGF) at the surgical site and by quantification of vessels in chicken’s chorioallantoic membrane (CAM), treated with AR 500 μg/ml for 48 h. Results: On the fifth day, eyes of RA group displayed higher bleb area (3.6 ± 0.2 versus 1.8 ± 0.2; p = 0.004) and lower vascularity (3.0 ± 0.5 versus 4.0 ± 0.4; p = 0.009) than controls; however, difference in IOP reduction was not significant (−1.4 ± 0.3 versus −0.8 ± 0.3 mmHg; p = 0.226). Proportion of vessels/field (4.6 ± 0.5 versus 10.4 ± 0.9; p = 0.008) and VEGF immunostaining (15,347 ± 3788 versus 31,043 ± 3230; p = 0.019) also declined with RA treatment. However, at the 15th day, none of the parameters were different between the groups, except for vessels/field proportion (5.4 ± 1.0 versus 10.6 ± 1.6; p = 0.035). CAM exposed to AR inhibited vascularization (−45.67 ± 4.74%; p < 0.001). Conclusion: These data indicate RA has a short-term anti-angiogenic effect and could be a potential modulator of neovascularization during subconjunctival healing at glaucoma filtration surgical sites.
A prospective, randomized, double blinded comparison of intranasal dexmedetomodine vs intranasal ketamine in combination with intravenous midazolam for procedural sedation in school aged children undergoing MRI

Background: For optimum magnetic resonance imaging (MRI) image quality and to ensure precise diagnosis, patients have to remain motionless. We studied the effects of intranasal dexmedetomidine and ketamine with intravenous midazolam for pre-procedural and procedural sedation in school aged children. Patients and Methods: Children were randomly allocated to one of two groups: (Group D) received intranasal dexmedetomidine 3 μg kg–1 and (Group K) received intranasal ketamine 7 mg kg–1. Sedation levels 10, 20 and 30 min after drug instillation were evaluated using a Modified Ramsay sedation scale. A 4-point score was used to evaluate patients when they were separated from their parents and their response to intravenous cannulation. Results: The two groups were comparable in terms of the child's anxiety at presentation (P = 0.245). We observed that Group K achieved faster sedation at 10 min point with P < 0.05. A comparable sedation score at 20 and 30 min were noted. The two groups were comparable regarding to the child's acceptance of nasal administration (P = 0.65). The sedation failure rate was insignificantly differ between groups (13.7% vs. 20.6% for Group D and K respectively). Heart rate and systolic blood pressure showed a significant difference between the two groups starting from the point of 20 min. Conclusion: Intranasal dexmedetomidine 3 μg kg–1 or ketamine 7 mg kg–1 can be used safely and effectively to induce a state of moderate conscious sedation and to facilitate parents’ separation and IV cannulation. Addition of midazolam in a dose not sufficient alone to produce the target sedation achieved our goal of deep level of sedation suitable for MRI procedure.
The insulin signalling pathway in skeletal muscle : in silico and in vitro

Insulin signalling pathway plays an essential role in the maintenance of the glucose homeostasis. It has therefore been studied for decades for identifying the intermediates and their interactions. However, our understanding of the key mechanisms in insulin signalling and how the insulin signalling interfaces with the GLUT4 storage compartments are still limited. In this chapter, we use a data-hypothesis driven modelling approach to study the missing regulations in the insulin signalling pathway that describe the core dynamic behaviour of the insulin signalling pathway from insulin receptor to GLUT4 translocation. 14 Chapter 2. Systems biology approach to study the dynamics of the insulin signalling pathway
Dexmedetomidine and fentanyl combination for procedural sedation in a case of Duchenne muscular dystrophy

Duchenne muscular dystrophy, an X-linked disorder characterized by progressive muscle weakness, is the most common muscular dystrophy among children leading to death before the end of third decade. Anesthesia in such patients pose a great challenge due to various complications associated with it. The dreaded metabolic and clinical complications occur due to various inhalational anesthetics and succinylcholine in this subset of patients. We are reporting a child with diagnosed Duchenne muscular dystrophy who underwent excision of dentigerous cyst in oral cavity under procedural sedation with combination of dexmedetomidine and fentanyl and thus administration of general anesthesia was avoided.
Pediatric Emergency Departments are More Likely Than General Emergency Departments to Treat Asthma Exacerbation With Systemic Corticosteroids

Objective. To determine whether systemic corticosteroids are under-prescribed (as measured by current NIH treatment guidelines) for children in the United States seen in the emergency department (ED) for acute asthma, and to identify factors associated with prescribing systemic corticosteroids. Methods. We used data from the 2001–2007 National Hospital Ambulatory Medical Care Survey. The study population was children ≤18 years old in the ED with a primary diagnosis of asthma (ICD-9-CM code 493.xx) who received bronchodilator(s). The primary outcome was receipt of a systemic corticosteroid in the ED. Independent variables included patient-level (e.g., demographics, insurance, fever, admission), physician-level (provider type, ancillary medications and tests ordered), and system-level factors (e.g., ED type, geographic location, time of day, season, year). We used multivariable logistic regression techniques to identify factors associated with systemic corticosteroid treatment. Results. Systemic corticosteroids were prescribed at only 63% of pediatric acute asthma visits to EDs. Over the study period, there was a trend toward increasing systemic corticosteroid use (p for trend = .05). After adjusting for potential confounders, patients were more likely to receive systemic corticosteroids when treated in pediatric EDs than in general EDs (OR = 2.45; 95% CI: 1.26–4.77). Conclusion. Systemic corticosteroids are under-prescribed for children who present to EDs with acute asthma exacerbations. Pediatric EDs are more likely than general EDs to treat asthma exacerbations with systemic corticosteroids. Differences in the process of care in pediatric ED settings (compared to general EDs) may increase the likelihood of adherence to NIH treatment guidelines.
Insulin sensitivity affects corticolimbic brain responses to visual food cues in polycystic ovary syndrome patients

Abstract Background: This study examined the effect of insulin sensitivity on the responsiveness of appetite regulatory brain regions to visual food cues. Materials and methods: Nineteen participants diagnosed with polycystic ovary syndrome (PCOS) were divided into insulin-sensitive (n=8) and insulin-resistant (n=11) groups based on the homeostatic model assessment of insulin resistance (HOMA2-IR). Subjects underwent functional magnetic resonance imaging (fMRI) while viewing food pictures following water or dextrose consumption. The corticolimbic blood oxygen level dependent (BOLD) responses to high-calorie (HC) or low-calorie (LC) food pictures were compared within and between groups. Results: BOLD responses to food pictures were reduced during a glucose challenge in numerous corticolimbic brain regions in insulin-sensitive but not insulin-resistant subjects. Furthermore, the degree of insulin resistance positively correlated with the corticolimbic BOLD response in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate and ventral tegmental area (VTA) in response to HC pictures, and in the dorsolateral prefrontal cortex (DLPFC), mPFC, anterior cingulate, and insula in response to LC pictures following a glucose challenge. BOLD signal in the OFC, midbrain, hippocampus, and amygdala following a glucose challenge correlated with HOMA2-IR in response to HC-LC pictures. Conclusion: We conclude that the normal inhibition of corticolimbic brain responses to food pictures during a glucose challenge is compromised in insulin-resistant subjects. The increase in brain responsiveness to food pictures during postprandial hyperinsulinemia may lead to greater non-homeostatic eating and perpetuate obesity in insulin-resistant subjects.