Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers.

Background: Thyroid nodules are an extremely common entity, and surgery is considered the ultimate diagnostic strategy in those with unclear malignant potential. Unfortunately, strategies aiming to predict the risk of malignancy have inadequate specificity. Our group recently found that the microenvironment of thyroid cancer is characterized by an enhanced immune invasion and activated immune response mediated by double-negative T lymphocytes (DN T) (CD3+CD4-CD8-), which are believed to enable or promote tumorigenesis. In the present work, we try to use the DN T cells' proportion in thyroid fine-needle aspiration (FNA) material as a predictor of the risk of malignancy. Methods: We recruited 127 patients and obtained ultrasound-guided FNA samples from subjects with cytology-positive or suspicious for malignancy and from those with benign nodular goiter associated with compressive symptoms (such as dysphagia, shortness of breath, or hoarseness), Hashimoto thyroiditis, and Graves' disease. Out of 127, we investigated 46 FNA samples of patients who underwent total thyroidectomy and for which postoperative histological diagnosis by the academic pathologists was available. We specifically measured the number of cells expressing CD3+CD4-CD8- (DN T) as a function of total CD3+ cells in FNA samples using flow cytometry. We correlated their FNA DN T-cell proportions with the pathological findings. Results: The DN T cells were significantly more abundant in lymphocytic infiltrates of thyroid cancer cases compared to benign nodule controls (p < 0.0001). When the DN T-cell population exceeded a threshold of 9.14%, of total CD3+ cells, the negative likelihood ratio of being cancer-free was 0.034 (96.6% sensitivity, 95% CI, 0.915-1.000, p < 0.0001). DN T cells at <9.14% were not found in any subject with benign disease (specificity 100%). The high specificity of the test is promising, since it abolishes a false-positive diagnosis and in turn unnecessary surgical procedures. Conclusion: The present study proposes DN T cells' proportion as a preoperative diagnostic signature for thyroid cancer that with integration of RNA transcriptomics can provide a simplified technology based on the PCR assay for the ease of operation.

COVID-19 in Africa: Survey Analysis of Impact on Health-Care Workers.

As coronavirus disease 2019 (COVID-19) spreads across Africa, little is known about the impact of the pandemic on health-care workers (HCWs) in the region. We designed an anonymous survey distributed via e-mail and phone messaging to 13 countries through the African Hepatitis B Network. We obtained 489 analyzable responses. We used risk ratio analysis to quantify the relationship between binary variables and χ2 testing to quantify the statistical significance of these relationships. Median age of respondents was 30 years (interquartile range, 26-36 years) and 63% were physicians. The top three sources of information used by HCWs for COVID-19 management included the Ministry of Health of each country, the WHO, and social media. Forty-nine percent reported a decrease in income since the start of the pandemic, with the majority experiencing between a 1% and a 25% salary reduction. Sixty-six percent reported some access to personal protective equipment; only 14% reported appropriate access. Moreover, one third of respondents reported no availability of ventilators at their facility. Strikingly, the percentage of HCWs reporting never feeling depressed changed from 61% before the pandemic to 31% during the pandemic, with a corresponding increase in daily depressive symptoms from 2% to 20%. Most respondents (> 97%) correctly answered survey questions about COVID-19 symptoms, virus transmission, and prevention. Our survey revealed African HCWs face a variety of personal and professional context-dependent challenges. Ongoing support of HCWs through and after the COVID-19 pandemic is essential.

Risk of Healthcare Worker Burnout in Africa during the COVID-19 Pandemic.

COVID-19 is now impacting every country in Africa and healthcare workers (HCWs) across the continent remain susceptible to professional burnout. We designed a 43-question survey addressing multiple aspects of the COVID-19 pandemic. The survey was anonymous, distributed via email and phone messaging to 13 countries in Africa. We obtained 489 analyzable responses. 49% off HCWs reported a decrease in income, with the majority experiencing between 1-25% salary reduction. Sixty-six percent reported some access to personal protective equipment (PPE), 20% had no access to PPE and only 14% reported proper access. Strikingly, the percentage reporting never feeling depressed changed from 61% before the pandemic to 31% during the pandemic, with an increase in daily depression from 2% to 20%. We found no association between depression and change in income, household size, availability of PPE or lockdown. Safety concerns related to stigma from being HCWs affected 56% of respondents.

Creating opportunities for occupational development using the concerns report method.

BACKGROUND: Little research has focused on working with communities to promote and support children's occupational development. AIM/OBJECTIVE: We used the Concerns Report Method (CRM) to identify community supports for parents with young children that could enhance children's occupational development. MATERIAL AND METHOD: We conducted interviews/focus groups with parents (n = 29) and service providers (n = 11). We used content analysis to identify four themes: availability, barriers and facilitators, parent/child transitions, and making connections. The themes were used to create a concerns report survey for parents and service providers. A random sample of parents (n = 319) and convenience sample of service providers (n = 47) in one community area of a Canadian urban center completed the on-line survey. We held a community forum to review the results and identify solutions for action. RESULTS: Parents' highest priorities included childcare, supports in community schools, preschool programs, and supports in one location. Service providers highest priorities included: identification of developmental concerns; parenting education; programs for fathers, programs that offer child care, a doctor, and child care. CONCLUSIONS: Service providers need to engage parents and consider parents' perspectives when planning services to ensure community supports will meet parent identified needs. SIGNIFICANCE: Using community-based participatory research approaches, occupational therapists can contribute to children's occupational development.

Recurrence of Graves' disease in ectopic thyroid tissue.

A 40-year-old woman with a history of Graves' disease status postorbital decompression for severe ophthalmopathy underwent total thyroidectomy by a high volume thyroid surgeon in July 2013 with a benign final pathology. Eight months later, she presented with a mass on the right anterior neck that showed minimal growth over time. Her thyroid stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels were consistently elevated and increasing. She underwent removal of the neck mass in September 2016. Final pathology showed benign thyroid tissue with diffuse hyperplasia and lymphoid follicles, consistent with Graves' disease. We present an unusual recurrence of Graves' disease post-total thyroidectomy that recurred secondary to ectopic thyroid tissue in the right upper anterior neck deep to the strap muscles.

Rare DNA copy number variants in cardiovascular malformations with extracardiac abnormalities.

Clinically significant cardiovascular malformations (CVMs) occur in 5-8 per 1000 live births. Recurrent copy number variations (CNVs) are among the known causes of syndromic CVMs, accounting for an important fraction of cases. We hypothesized that many additional rare CNVs also cause CVMs and can be detected in patients with CVMs plus extracardiac anomalies (ECAs). Through a genome-wide survey of 203 subjects with CVMs and ECAs, we identified 55 CNVs >50 kb in length that were not present in children without known cardiovascular defects (n=872). Sixteen unique CNVs overlapping these variants were found in an independent CVM plus ECA cohort (n=511), which were not observed in 2011 controls. The study identified 12/16 (75%) novel loci including non-recurrent de novo 16q24.3 loss (4/714) and de novo 2q31.3q32.1 loss encompassing PPP1R1C and PDE1A (2/714). The study also narrowed critical intervals in three well-recognized genomic disorders of CVM, such as the cat-eye syndrome region on 22q11.1, 8p23.1 loss encompassing GATA4 and SOX7 and 17p13.3-p13.2 loss. An analysis of protein-interaction databases shows that the rare inherited and de novo CNVs detected in the combined cohort are enriched for genes encoding proteins that are direct or indirect partners of proteins known to be required for normal cardiac development. Our findings implicate rare variants such as 16q24.3 loss and 2q31.3-q32.1 loss, and delineate regions within previously reported structural variants known to cause CVMs.

Variability of global left ventricular deformation analysis using vendor dependent and independent two-dimensional speckle-tracking software in adults.

BACKGROUND: Evaluation of myocardial deformation by two-dimensional speckle-tracking is useful for clinical and research purposes. However, differences may exist among different ultrasound machines, software packages, frame rates, and observers. METHODS: Thirty patients underwent echocardiography on both GE (Vivid 9; GE Vingmed Ultrasound AS, Horten, Norway) and Philips (iE33; Philips Ultrasound, Bothell, WA) ultrasound systems. From each study, two sets of images were stored in Digital Imaging and Communications in Medicine format, optimized for strain evaluation: one set of images at the acquisition frame rate (55-90 frames/sec) and one set of images at a compressed frame rate of 30 frames/sec. Vendor-independent software (VIS; TomTec 2D Cardiac Performance Analysis, Munich, Germany) was used to measure strain in multiple directions and was compared with vendor-specific software (GE EchoPAC; GE Vingmed Ultrasound AS). RESULTS: Intraobserver and interobserver coefficients of variation ranged from 5.5% to 8.7% for longitudinal strain, from 10.7% to 20.8% for circumferential, and from 15.3% to 33.4% for radial and transverse strain. Strain values obtained using VIS were comparable with those obtained using vendor-specific software for longitudinal strain, regardless of ultrasound machine or frame rate. For circumferential strain, a consistent large bias was observed between VIS and vendor-specific software, with higher values using VIS. Slightly higher strain values were observed by analysis at the acquisition frame rate compared with the low frame rate, but no consistent bias was observed between images from different vendors. CONCLUSIONS: Global longitudinal strain consistently showed good reproducibility, while reproducibility was moderate for circumferential strain and poor in the radial direction. Retrospective analysis of legacy Digital Imaging and Communications in Medicine data at 30 frames/sec can be reliably performed for longitudinal strain.

Gastrointestinal staple line reinforcement.

Gastrointestinal resections and anastomoses are commonly performed using stapling devices in a wide range of open and laparoscopic procedures. Whether they are hand-sewn or stapled, anastomoses have an associated leak rate that can impart significant morbidity or mortality to a procedure. In addition, bleeding from staple lines can cause additional complications. Staple line reinforcement is one intervention that has been postulated to reduce both the leak rate and associated bleeding risk. This can be accomplished with either material applied exogenously to the staple line, as in an engineered absorbable biomaterial, or it may use a material - either absorbable or nonabsorbable - that is incorporated into the staple line. A number of reinforcements are currently available but all add time and cost to the procedures in which they are used. However, preventing the complications associated with leak and hemorrhage from staple lines may justify the added cost of these devices. A review of the available published literature was performed to review the current data pertaining to the reinforcement of living tissue and anastomoses with these various reinforcements available to surgeons.

A comparison of terahertz pulsed imaging with transmission microradiography for depth measurement of enamel demineralisation in vitro.

Terahertz pulsed imaging (TPI) is a relatively new, non-ionising and non-destructive imaging technique for studying hard tissues which does not require tooth section preparation, unlike transmission microradiography (TMR). If TPI can measure the depths of caries/demineralisation lesions accurately the same tooth samples could be reused and remeasured during in vitro and in situ studies on de- and/or re-mineralisation. The aim of this study was to compare TPI and TMR for measuring the depths of a range of artificially induced bovine enamel demineralised lesions in vitro. Bovine slabs with artificial caries, induced to different levels of demineralisation by two different but standard demineralisation techniques ('acid gel' and 'carbopol') were measured by TPI and TMR and the readings compared. The set of TPI/TMR measurements obtained on the gel-demineralised slabs showed an extremely high coefficient of determination (r(2) = 0.995). Detailed analysis of the results and theoretical considerations (involving the relationship between refractive index profiling and mineral loss profile) are used to explain the findings and show that for acid gel lesions TPI is measuring demineralisation in the range of 47% of that of TMR depth plus an intercept of 16 microm, with further calculations allowing the TMR depths to be determined to within 5% using TPI.