Recertification guidelines for Massachusetts educators

The incorporation of the extracellular matrix (ECM) is essential for generating in vitro models that truly represent the microarchitecture found in human tissues. However, the cell-cell and cell-ECM interactions in vitro remains poorly understood in placental trophoblast biology. We investigated the effects of varying the surface properties (surface thickness and stiffness) of two ECMs, collagen I and Matrigel, on placental trophoblast cell morphology, viability, proliferation, and expression of markers involved in differentiation/syncytial fusion. Most notably, thicker Matrigel surfaces were found to induce the self-assembly of trophoblast cells into 3D spheroids that exhibited thickness-dependent changes in viability, proliferation, syncytial fusion, and gene expression profiles compared to two-dimensional cultures. Changes in F-actin organization, cell spread morphologies, and integrin and matrix metalloproteinase gene expression profiles, further reveal that the response to surface thickness may be mediated in part through cellular stiffness-sensing mechanisms. Our derivation of self-assembling trophoblast spheroid cultures through regulation of ECM surface alone contributes to a deeper understanding of cell-ECM interactions, and may be important for the advancement of in vitro platforms for research or diagnostics

Antibiotic Resistance and its Association with Biocides Susceptibilities among Microbial Isolates in an Egyptian Hospital

Background: Recently there has been a growing concern that the indiscriminate use of antimicrobial agents in the household, food industry and in hospitals may contribute to the emergence of bacteria resistant to antibiotics.Aim of the work: To detect any possible link between the susceptibility profiles of different clinical and environmental isolates to biocides and antibiotics in an Egyptian hospital.Methods: 66 different microbial isolates were isolated from different clinical specimens and different environmental samples obtained from a University Hospital in Alexandria. These isolates were screened for their susceptibility to 22 broad spectrum antibiotics using disc agar diffusion technique. Also the susceptibility of the isolates to 6 commonly used biocides was screened through MIC determination by agar dilution technique. Correlations between the obtained data were made through Spearman’s correlation using SPSS® Statistical program.Results: 62% of the isolates were multidrug resistant (MDR); and 11% were extremely drug resistant (XDR). On the other hand, 34% of the tested isolates were multi-disinfectant reduced susceptibility (MDRS) isolates. The statistical analysis of the obtained data revealed a moderate positive correlation between antibiotic resistance and biocide tolerance (0.376≥Ï≥0.278, p<0.05). In addition, strong significant correlations (p<0.01) were also found between reduced susceptibilities to multiple biocides such as benzalkonium chloride (BK), cetrimide (CET), chlorhexidine (CHX), povidone-iodine (PVPI) and Dettol®.Conclusion: Cross-resistance between biocides and antibiotics can aggravate the existing problem of antibiotic resistance in hospitals

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

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

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

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Exploring the role of tumour microenvironment in the behaviour of breast ductal carcinoma in situ

Background: Breast ductal carcinoma in situ (DCIS) accounts for more than 20% of screen-detected breast cancer. To date, predictors of DCIS behaviour are not well defined. Tumour microenvironment (TME) plays a role in tumour progression; therefore, the aim of the current study was to characterise a large cohort of DCIS with long term follow-up data and to decipher the role of TME in DCIS outcome. Patients and methods: This study includes 1,488 cases comprises pure DCIS (n=1,249) and DCIS associated with synchronous invasive carcinoma (n=239). Clinicopathological and outcome data was collected. All cases were histologically reviewed, and representative tumour blocks were retrieved. Tissue microarrays (TMAs) were constructed followed by molecular characterisation for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki67. Tumour infiltrating lymphocytes (TILs) were assessed using novel method and their association with local recurrence was investigated. Mining for biomarkers that regulate remodelling and degradation of the surrounding stroma and have potential prognostic values in DCIS was performed. This includes prolyl-4-hydroxylase Α subunit 2 (P4HA2), cathepsin A (CTSA), cathepsin V (CTSV), legumain (LGMN) and Collagen (XI) alpha-1 chain (COL11A1). The expression of these biomarkers was evaluated in the TMA using immunohistochemistry and their prognostic value was analysed. In addition, image analysis assessment of the geometric characterisation of collagen surrounding DCIS was performed and collagen prognostic index (CPI) was developed. Moreover, the role of hypoxia and centrosome amplification (CA) has been investigated. Results: There was a significant increase in the rate of breast conserving surgery (BCS) and the use of radiotherapy (RT) in DCIS management with time, along with a decline in the rate of re- excisions. Large size, high grade, and omission of adjuvant RT were independent predictors of the development of ipsilateral local recurrence. The highest proportion (60%) of cases were of Luminal A subtype, and the lowest attribution (11%) was for HER2 positive tumours. HER2 positive and Triple Negative subtypes were of larger tumour size, higher grade, and more frequently treated with mastectomy. Dense TILs were associated with adverse clinicopathological parameters and high recurrence rate. DCIS associated with synchronous invasive carcinoma showed higher TILs density than pure DCIS. The assessment of the selected biomarker panel revealed a significant difference in their protein expression between pure DCIS and those associated with invasion. An independent association between high expression of P4HA2, CTSA, CTSV, LGMN and COL11A1 with the development of local recurrence was observed. DCIS with high CPI and harbouring higher structural and/or numerical centrosomal aberrations were associated poor outcome. Conclusions: This study shows that TME plays a key role in DCIS behaviour and outcome. In addition to the conventional clinicopathological variables, dense TILs, high expression of P4HA2, CTSA, CTSV, LGMN, COL11A1, high CPI and centrosomal aberrations were independent predictors of DCIS outcome. These variables could potentially be used in combination to refine the prognostic stratification of DCIS patients in routine practice

Exploring the role of tumour microenvironment in the behaviour of breast ductal carcinoma in situ

Background: Breast ductal carcinoma in situ (DCIS) accounts for more than 20% of screen-detected breast cancer. To date, predictors of DCIS behaviour are not well defined. Tumour microenvironment (TME) plays a role in tumour progression; therefore, the aim of the current study was to characterise a large cohort of DCIS with long term follow-up data and to decipher the role of TME in DCIS outcome. Patients and methods: This study includes 1,488 cases comprises pure DCIS (n=1,249) and DCIS associated with synchronous invasive carcinoma (n=239). Clinicopathological and outcome data was collected. All cases were histologically reviewed, and representative tumour blocks were retrieved. Tissue microarrays (TMAs) were constructed followed by molecular characterisation for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki67. Tumour infiltrating lymphocytes (TILs) were assessed using novel method and their association with local recurrence was investigated. Mining for biomarkers that regulate remodelling and degradation of the surrounding stroma and have potential prognostic values in DCIS was performed. This includes prolyl-4-hydroxylase Α subunit 2 (P4HA2), cathepsin A (CTSA), cathepsin V (CTSV), legumain (LGMN) and Collagen (XI) alpha-1 chain (COL11A1). The expression of these biomarkers was evaluated in the TMA using immunohistochemistry and their prognostic value was analysed. In addition, image analysis assessment of the geometric characterisation of collagen surrounding DCIS was performed and collagen prognostic index (CPI) was developed. Moreover, the role of hypoxia and centrosome amplification (CA) has been investigated. Results: There was a significant increase in the rate of breast conserving surgery (BCS) and the use of radiotherapy (RT) in DCIS management with time, along with a decline in the rate of re- excisions. Large size, high grade, and omission of adjuvant RT were independent predictors of the development of ipsilateral local recurrence. The highest proportion (60%) of cases were of Luminal A subtype, and the lowest attribution (11%) was for HER2 positive tumours. HER2 positive and Triple Negative subtypes were of larger tumour size, higher grade, and more frequently treated with mastectomy. Dense TILs were associated with adverse clinicopathological parameters and high recurrence rate. DCIS associated with synchronous invasive carcinoma showed higher TILs density than pure DCIS. The assessment of the selected biomarker panel revealed a significant difference in their protein expression between pure DCIS and those associated with invasion. An independent association between high expression of P4HA2, CTSA, CTSV, LGMN and COL11A1 with the development of local recurrence was observed. DCIS with high CPI and harbouring higher structural and/or numerical centrosomal aberrations were associated poor outcome. Conclusions: This study shows that TME plays a key role in DCIS behaviour and outcome. In addition to the conventional clinicopathological variables, dense TILs, high expression of P4HA2, CTSA, CTSV, LGMN, COL11A1, high CPI and centrosomal aberrations were independent predictors of DCIS outcome. These variables could potentially be used in combination to refine the prognostic stratification of DCIS patients in routine practice