Scalable noninvasive amplicon-based precision sequencing (SNAPseq) for genetic diagnosis and screening of β-thalassemia and sickle cell disease using a next-generation sequencing platform

β-hemoglobinopathies such as β-thalassemia (BT) and Sickle cell disease (SCD) are inherited monogenic blood disorders with significant global burden. Hence, early and affordable diagnosis can alleviate morbidity and reduce mortality given the lack of effective cure. Currently, Sanger sequencing is considered to be the gold standard genetic test for BT and SCD, but it has a very low throughput requiring multiple amplicons and more sequencing reactions to cover the entire HBB gene. To address this, we have demonstrated an extraction-free single amplicon-based approach for screening the entire β-globin gene with clinical samples using Scalable noninvasive amplicon-based precision sequencing (SNAPseq) assay catalyzing with next-generation sequencing (NGS). We optimized the assay using noninvasive buccal swab samples and simple finger prick blood for direct amplification with crude lysates. SNAPseq demonstrates high sensitivity and specificity, having a 100% agreement with Sanger sequencing. Furthermore, to facilitate seamless reporting, we have created a much simpler automated pipeline with comprehensive resources for pathogenic mutations in BT and SCD through data integration after systematic classification of variants according to ACMG and AMP guidelines. To the best of our knowledge, this is the first report of the NGS-based high throughput SNAPseq approach for the detection of both BT and SCD in a single assay with high sensitivity in an automated pipeline

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Comparison of the bone-anchored pendulum appliance and the bone-anchored intraoral bodily molar distalizer: An original research

Introduction: With the advent of mini-implants, Class II correction has become routine. The study's goal was to compare the “Bone-Anchored Pendulum Appliance (BAPA)” to the “Bone-Anchored Intraoral Bodily Molar Distalizer (BAIBMD)” in terms of clinical efficacy. Materials and Procedures: Five boys and five girls were among the 10 patients in this split-mouth trial who had to have their molars distalized. On one side, BAPA Construction, and on the other, BAIBMD was piloted. A titanium mini-screw was used to secure both appliances to the bone since this was a spilled-mouth technique. The first molar bands to apply 200 g of force were used for both devices, as with all the other components that were similar for both appliances. For both sides, the nature, duration, and rate of tooth movement were compared. Using the Wilcoxon signed-rank test, descriptive statistics for several parameters were examined. Results: Distalization was accomplished on both sides with clinical success. The rate of distalization did not show any significant variation. Less time was needed for distalization with BAPA, as evidenced by the statistically substantial variances in treatment duration between the two groups. Molar tipping was noticed in BAPA, and it was statistically significant. Conclusion: While the pace of distalization was equal for both appliances, BAIBMD required more time than BAPA but resulted in a distal tooth movement that was mostly translatory in nature

Evaluation and Comparison of Thermal Changes in the Pulp Chamber in Different Inter Proximal Reduction Techniques: An In-vitro Study

Introduction: Interproximal reduction (IPR) is a common orthodontic treatment procedure that is used which involves tooth reduction, anatomic recontouring, and protecting permanent teeth proximal enamel surfaces. Sheridan described the air-rotor stripping technique as an alternative to extraction in borderline cases. Though there are many studies, it was not clearly differentiated regarding the pulpal temperature changes during IPR. Materials and Methods: In this in vitro study, 63 extracted human premolar teeth were randomly assigned to three groups (n=21). Group-1 (Strauss diamond stripping bur) at high speed above 20,000 rpm, Group-2 (Manual Handheld metal stripper). Group-3 (Strauss diamond stripping disc) at a low speed below 15,000 rpm. The average mean temperature is assessed for each tooth during various techniques using K-type thermocouple. During the procedure, the thermometer display was covered, and the temperature was revealed after all the stripping procedures had already been performed. Data were analyzed using IBM SPSS version 20 software. Descriptive statistics, one way analysis of variance with Tukey’s post hoc tests were done to analyze the study data. Results: The mean rise in temperature was highest with disc &amp; micromotor (4.3ºC) followed by airotor &amp; bur (4.02ºC) and manual method (2.52ºC) (p ≤ 0.05). Conclusion: There was an increase in the pulpal temperature using diamond stripping disc with micromotor followed by the airotor and bur, manual hand held stripping

In-vitro Effectiveness of Herbal Mouthwashes on the Force Degradation of Two Orthodontic E-chains

Background: Plaque build-up around fixed orthodontic appliances might lead to clinical problems. Even though mouthwashes are recommended during orthodontic treatment, the magnitude of force loading and unloading in elastomeric chains is significantly affected by alcohol-containing mouthwashes. Aim: To evaluate and compare the efficacy of herbal mouthwashes on the force degradation of two orthodontic E-chains. Materials and Methods: Chlorhexidine, Hiora-K and Triphala were used in the study. Ninety pieces of closed clear E-chains with five loops each of AO and 3M companies were collected and divided into three groups (n=30) namely Chlorhexidine, Hiora-K and Triphala. Each group was divided into two sub-groups based on the E-chain brands (n=15). On day 1, the original force was recorded by stretching the E-chain up to 25mm using universal testing machine and the load was recorded in kilograms and converted to grams. The E-chains were subjected to their respective mouthwashes daily for one minute. The force was again recorded on the 21st and 30th days. The obtained data were subjected to statistical analysis using SPSS 16.0 version. Results: The 3M E-chain showed a significant(p=0.000) difference compared with AO. Hiora and Triphala showed lesser force degradation than Chlorhexidine (p=0.013). Further, there was a significant (p=0.001) reduction in force degradation from baseline to the first month. Conclusion: Force degradation was more significant from the1st to the 21st day. 3M E-chain showed less force decay than AO E-chain. Hiora-K and Triphala mouthwash groups showed less force decay than the Chlorhexidine

Correlation of Sagittal Skeletal malocclusion and Growth patterns between Digital and Conventional Dermatoglyphics

Background: The craniofacial morphology and its growth pattern are determined by the influence of various environmental factors depending on the genetic background. Due to the close association of MSX 1 and SMARCAD gene on the same chromosome, it can be hypothesized that malocclusion and fingerprint pattern are related. Furthermore, it is observed that the orofacial structures originate from the same embryonic tissue as the epidermal ridges, which are the ectoderm. Thus, the simultaneous development of the epidermal ridges and the orofacial structure during this time is deciphered and reflected in the fingerprint patterns. Aim: This study aimed to analyse, compare, and correlate the fingerprint patterns of individuals with different skeletal malocclusions and growth patterns using manual and digital methods. Materials and Methods: Patients (a random sample of 544) who were undergoing orthodontic treatment and were able to give informed consent were included in the study. Informed consent was obtained prior to the start of the procedure, with due regard to ethical issues and the confidentiality of fingerprint records. The anteroposterior jaw relation was determined from the patient's lateral cephalogram with evaluation of the parameters: SNA, ANB, SNB and growth patterns are determined using the mandibular plane angle according to Steiners analysis, the nature of the growth patterns, i.e., horizontal (HGP), Average (AGP) and vertical (VGP) growth pattern. Results: Individuals with loop patterns had a frequency of skeletal class I malocclusion, Whorl patterns with skeletal class II malocclusion, and Arch patterns with skeletal class III malocclusion. Consistent with the growth patterns, the whorl pattern was seen more prominently in the horizontal growth pattern, Arch pattern in the average growth pattern, and the loop pattern in the vertical growth pattern. Conclusion: Thus, the dermatoglyphics can be used as a screening tool for early prediction of skeletal malocclusion in a younger age group