Fluorescence guided surgery imaging systems for breast cancer identification: a systematic review.

Significance: Breast-conserving surgery (BCS) is limited by high rates of positive margins and re-operative interventions. Fluorescence-guided surgery seeks to detect the entire lesion in real time, thus guiding the surgeons to remove all the tumor at the index procedure. Aim: Our aim was to identify the optimal combination of a camera system and fluorophore for fluorescence-guided BCS. Approach: A systematic review of medical databases using the terms "fluorescence," "breast cancer," "surgery," and "fluorescence imaging" was performed. Cameras were compared using the ratio between the fluorescent signal from the tumor compared to background fluorescence, as well as diagnostic accuracy measures, such as sensitivity, specificity, and positive predictive value. Results: Twenty-one studies identified 14 camera systems using nine different fluorophores. Twelve cameras worked in the infrared spectrum. Ten studies reported on the difference in strength of the fluorescence signal between cancer and normal tissue, with results ranging from 1.72 to 4.7. In addition, nine studies reported on whether any tumor remained in the resection cavity (5.4% to 32.5%). To date, only three studies used the fluorescent signal for guidance during real BCS. Diagnostic accuracy ranged from 63% to 98% sensitivity, 32% to 97% specificity, and 75% to 100% positive predictive value. Conclusion: In this systematic review, all the studies reported a clinically significant difference in signal between the tumor and normal tissue using various camera/fluorophore combinations. However, given the heterogeneity in protocols, including camera setup, fluorophore studied, data acquisition, and reporting structure, it was impossible to determine the optimal camera and fluorophore combination for use in BCS. It would be beneficial to develop a standardized reporting structure using similar metrics to provide necessary data for a comparison between camera systems.

Biomedical applications of biodegradable polycaprolactone-functionalized magnetic iron oxides nanoparticles and their polymer nanocomposites.

Magnetic nanoparticles (MNPs) have gained significant attention among several nanoscale materials during the last decade due to their unique properties. These properties make them successful nanofillers for drug delivery and a number of new biomedical applications. MNPs are more useful when combined with biodegradable polymers. In this review, we discussed the synthesis of polycaprolactones (PCL) and the various methods of synthesizing magnetic iron oxide nanoparticles. Then, the synthesis of composites that is made of PCL and magnetic materials (with special focus on iron oxide nanoparticles) were highlighted. In addition, we comprehensively reviewed their application in drug delivery, cancer treatment, wound healing, hyperthermia, and bone tissue engineering. Other biomedical applications of the magnetic PCL such as mitochondria targeting are highlighted. Moreover, biomedical applications of magnetic nanoparticles incorporated into other synthetic polymers apart from PCL are also discussed. Thus, great progress and better outcome with functionalized MNPs enhanced with polycaprolactone has been recorded with the biomedical applications of drug delivery and recovery of bone tissues.

[Feasibility of MMPI-2-RF in patients with borderline intellectual functioning]. / Toepasbaarheid van de MMPI-2-RF bij patiënten met zwakbegaafdheid.

BACKGROUND: There are few psychometrically sound diagnostic instruments available to assess personality characteristics and psychopathology in patients with borderline intellectual functioning (BIF). It is important to assess personality characteristics and psychopathology in this target group because of their high risk on psychopathology. AIM: To determine whether the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is feasible in patients with BIF (Verbal Comprehension Index = 70-85) and psychopathology. METHOD: We examined scores on validity scales of the MMPI-2-RF of patients with BIF and compared these scores to those of a matched group of individuals with average intellectual functioning without psychopathology. RESULTS: Scores on the validity scales indicated that patients with BIF can report in a consistent and valid way about their complaints and personality characteristics. Compared to the comparison group they reported equally consistent and showed significantly more psychopathology. CONCLUSION: The MMPI-2-RF is feasible in the assessment of personality characteristics and psychopathology in patients with BIF..

Plants, public health and the pandemic.

At the onset of the pandemic, people resort to coping mechanisms to lessen the impact of social distancing enforced through quarantine protocols. Confined to their homes, despite recent relaxation of mobility and travel sanctions, many people find comfort and psychological reassurance in plant tending and gardening. Plants have been known for their medicinal and recreational purposes and their psychological therapeutic value. In the case of the Philippines, plant parenting has become a viral phenomenon.

Development and validation of a patient face-mounted, negative-pressure antechamber for reducing exposure of healthcare workers to aerosolized particles during endonasal surgery.

OBJECTIVE: The authors developed a negative-pressure, patient face-mounted antechamber and tested its efficacy as a tool for sequestering aerated particles and improving the safety of endonasal surgical procedures. METHODS: Antechamber prototyping was performed with 3D printing and silicone-elastomer molding. The lowest vacuum settings needed to meet specifications for class I biosafety cabinets (flow rate ≥ 0.38 m/sec) were determined using an anemometer. A cross-validation approach with two different techniques, optical particle sizing and high-speed videography/shadowgraphy, was used to identify the minimum pressures required to sequester aerosolized materials. At the minimum vacuum settings identified, physical parameters were quantified, including flow rate, antechamber pressure, and time to clearance. RESULTS: The minimum tube pressures needed to meet specifications for class I biosafety cabinets were -1.0 and -14.5 mm Hg for the surgical chambers with ("closed face") and without ("open face") the silicone diaphragm covering the operative port, respectively. Optical particle sizing did not detect aerosol generation from surgical drilling at these vacuum settings; however, videography estimated higher thresholds required to contain aerosols, at -6 and -35 mm Hg. Simulation of surgical movement disrupted aerosol containment visualized by shadowgraphy in the open-faced but not the closed-faced version of the mask; however, the closed-face version of the mask required increased negative pressure (-15 mm Hg) to contain aerosols during surgical simulation. CONCLUSIONS: Portable, negative-pressure surgical compartments can contain aerosols from surgical drilling with pressures attainable by standard hospital and clinic vacuums. Future studies are needed to carefully consider the reliability of different techniques for detecting aerosols.

COVID-19: back to healthcare basics in Philippine prisons.

Prisons have not escaped the effects of COVID-19. In countries where there are limited resources and spaces available, there is a need to find innovative ways to keep detainees safe and healthy. We can see various approaches such as the Irish model, which gives due importance to the establishment of contact tracing teams (CTT). In the case of Philippine prisons with high congestion rates, however, we may have to go back to certain healthcare basics to address COVID-19 transmissions.

ChurchInAction: the role of religious interventions in times of COVID-19.

In a recently published letter to the editor of this journal, the authors have called for the need to establish psychological support structures that cater to people's mental health in this time of the coronavirus disease 2019 pandemic. To be more holistic, we extend this call to include people's spiritual well-being as well. We highlight the initiatives of the Philippines' religious sector. In particular, we report some of the interventions made by the Roman Catholic Church that have led to the social media hashtag, #ChurchInAction. These religious and spiritual interventions showcase the efforts of the Philippine Church and play an important role in providing assistance in time of public health crisis.

[Suicide in individuals with mild intellectual disabilities]. / Suïcide bij mensen met een lichte verstandelijke beperking.

BACKGROUND: Little is known about suicide among individuals with mild intellectual disabilities (mid).
AIM: To explore risk factors for suicide among a small group of clients with mid who committed suicide.
METHOD: Case files of 11 clients with mid were analysed using the Integrated Motivational Volitional model.
RESULTS: Most suicides seem to have taken place impulsively and not on the basis of a predetermined plan. Most clients had comorbid mental health problems, predominantly trauma-related, impulse control and externalizing behavioural problems. The (imminent) loss of contact, such as in the case of transfer from one ward to another ward or to a facility, seems an important risk factor for suicide.
CONCLUSION: Clients with mid residing in a treatment facility may have an increased risk of suicide because of an interaction between client characteristics and treatment context.

Single-cell analysis of cardiogenesis reveals basis for organ-level developmental defects.

Organogenesis involves integration of diverse cell types; dysregulation of cell-type-specific gene networks results in birth defects, which affect 5% of live births. Congenital heart defects are the most common malformations, and result from disruption of discrete subsets of cardiac progenitor cells1, but the transcriptional changes in individual progenitors that lead to organ-level defects remain unknown. Here we used single-cell RNA sequencing to interrogate early cardiac progenitor cells as they become specified during normal and abnormal cardiogenesis, revealing how dysregulation of specific cellular subpopulations has catastrophic consequences. A network-based computational method for single-cell RNA-sequencing analysis that predicts lineage-specifying transcription factors2,3 identified Hand2 as a specifier of outflow tract cells but not right ventricular cells, despite the failure of right ventricular formation in Hand2-null mice4. Temporal single-cell-transcriptome analysis of Hand2-null embryos revealed failure of outflow tract myocardium specification, whereas right ventricular myocardium was specified but failed to properly differentiate and migrate. Loss of Hand2 also led to dysregulation of retinoic acid signalling and disruption of anterior-posterior patterning of cardiac progenitors. This work reveals transcriptional determinants that specify fate and differentiation in individual cardiac progenitor cells, and exposes mechanisms of disrupted cardiac development at single-cell resolution, providing a framework for investigating congenital heart defects.

Oligogenic inheritance of a human heart disease involving a genetic modifier.

Complex genetic mechanisms are thought to underlie many human diseases, yet experimental proof of this model has been elusive. Here, we show that a human cardiac anomaly can be caused by a combination of rare, inherited heterozygous mutations. Whole-exome sequencing of a nuclear family revealed that three offspring with childhood-onset cardiomyopathy had inherited three missense single-nucleotide variants in the MKL2, MYH7, and NKX2-5 genes. The MYH7 and MKL2 variants were inherited from the affected, asymptomatic father and the rare NKX2-5 variant (minor allele frequency, 0.0012) from the unaffected mother. We used CRISPR-Cas9 to generate mice encoding the orthologous variants and found that compound heterozygosity for all three variants recapitulated the human disease phenotype. Analysis of murine hearts and human induced pluripotent stem cell-derived cardiomyocytes provided histologic and molecular evidence for the NKX2-5 variant's contribution as a genetic modifier.

Experiences of facilitators regarding the extended curriculum programme offered at a higher education institution in the province of KwaZulu-Natal in South Africa.

BACKGROUND:  Much like the rest of the world, student access and success are primary concerns of the South African higher education institutions, especially in the face of data that suggest that up to 50% of students do not successfully complete their course of study. Despite compulsory and free basic education for all South Africans, and increased government funding for education, there has been little impact on learner performance and the majority of primary schools remain poor. To improve access and success and in keeping with international practice, the Department of Nursing at the selected university of technology in 2013 offered for the first time the extended curriculum programme (ECP). To date, the impact of the programme has never been evaluated. OBJECTIVES:  The aim of the study was to explore the experiences of the facilitators regarding ECP in the undergraduate nursing programme. METHOD:  Guided by this, the current article describes a qualitative exploration of the experiences of six purposively selected facilitators regarding ECP in the Department of Nursing. In-depth interviews were conducted with the ECP facilitators. Tesch's method was used to analyse the data. RESULTS:  Four main themes emerged from the data: stigmatisation and lack of confidence, lack of self-will, additional workload of facilitators and gradual improvement of students' performance. The participants reported that although students displayed and verbalised negative attitude towards the ECP, the performance of students showed gradual improvement and thus a need to continue to offer the programme to increase access and success in higher education institutions. CONCLUSION:  It was concluded that ECP should continue to increase access and success in higher education institutions; however, there is a need for additional resources to support ECP students.

Childhood Bullying: Implications for Physicians.

Childhood bullying is common and can lead to serious adverse physical and mental health effects for both the victim and the bully. In teenagers, risk factors for becoming a victim of bullying include being lesbian, gay, bisexual, or transgender; having a disability or medical condition such as asthma, diabetes mellitus, a skin condition, or food allergy; or being an outlier in weight and stature. An estimated 20% of youth have been bullied on school property, and 16% have been bullied electronically in the past year. Bullying can result in emotional distress, depression, anxiety, social isolation, low self-esteem, school avoidance/refusal, and substance abuse for the victim and the bully. Preventive measures include encouraging patients to find enjoyable activities that promote confidence and self-esteem, modeling how to treat others with kindness and respect, and encouraging patients to seek positive friendships. For those who feel concern or guilt about sharing their experiences, it may be useful to explain that revealing the bullying may not only help end the cycle for them but for others as well. Once bullying has been identified, family physicians have an important role in screening for its harmful effects, such as depression and anxiety. A comprehensive, multitiered approach involving families, schools, and community resources can help combat bullying. Family physicians are integral in recognizing children and adolescents who are affected by bullying-as victims, bullies, or bully- victims-so they can benefit from the intervention process.

BET bromodomain inhibition suppresses innate inflammatory and profibrotic transcriptional networks in heart failure.

Despite current standard of care, the average 5-year mortality after an initial diagnosis of heart failure (HF) is about 40%, reflecting an urgent need for new therapeutic approaches. Previous studies demonstrated that the epigenetic reader protein bromodomain-containing protein 4 (BRD4), an emerging therapeutic target in cancer, functions as a critical coactivator of pathologic gene transactivation during cardiomyocyte hypertrophy. However, the therapeutic relevance of these findings to human disease remained unknown. We demonstrate that treatment with the BET bromodomain inhibitor JQ1 has therapeutic effects during severe, preestablished HF from prolonged pressure overload, as well as after a massive anterior myocardial infarction in mice. Furthermore, JQ1 potently blocks agonist-induced hypertrophy in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Integrated transcriptomic analyses across animal models and human iPSC-CMs reveal that BET inhibition preferentially blocks transactivation of a common pathologic gene regulatory program that is robustly enriched for NFκB and TGF-ß signaling networks, typified by innate inflammatory and profibrotic myocardial genes. As predicted by these specific transcriptional mechanisms, we found that JQ1 does not suppress physiological cardiac hypertrophy in a mouse swimming model. These findings establish that pharmacologically targeting innate inflammatory and profibrotic myocardial signaling networks at the level of chromatin is effective in animal models and human cardiomyocytes, providing the critical rationale for further development of BET inhibitors and other epigenomic medicines for HF.

Progress and Perspectives on HIV-1 microbicide development.

The majority of HIV-1 infections occur via sexual intercourse. Women are the most affected by the epidemic, particularly in developing countries, due to their socio-economic dependence on men and the fact that they are often victims of gender based sexual violence. Despite significant efforts that resulted in the reduction of infection rates in some countries, there is still need for effective prevention methods against the virus. One of these methods for preventing sexual transmission in women is the use of microbicides. In this review we provide a summary of the progress made toward the discovery of affordable and effective HIV-1 microbicides and suggest future directions. We show that there is a wide range of compounds that have been proposed as potential microbicides. Although most of them have so far failed to show protection in humans, there are many promising ones currently in pre-clinical studies and in clinical trials.

Cardiac Stem Cell Hybrids Enhance Myocardial Repair.

RATIONALE: Dual cell transplantation of cardiac progenitor cells (CPCs) and mesenchymal stem cells (MSCs) after infarction improves myocardial repair and performance in large animal models relative to delivery of either cell population. OBJECTIVE: To demonstrate that CardioChimeras (CCs) formed by fusion between CPCs and MSCs have enhanced reparative potential in a mouse model of myocardial infarction relative to individual stem cells or combined cell delivery. METHODS AND RESULTS: Two distinct and clonally derived CCs, CC1 and CC2, were used for this study. CCs improved left ventricular anterior wall thickness at 4 weeks post injury, but only CC1 treatment preserved anterior wall thickness at 18 weeks. Ejection fraction was enhanced at 6 weeks in CCs, and functional improvements were maintained in CCs and CPC+MSC groups at 18 weeks. Infarct size was decreased in CCs, whereas CPC+MSC and CPC parent groups remained unchanged at 12 weeks. CCs exhibited increased persistence, engraftment, and expression of early commitment markers within the border zone relative to combinatorial and individual cell population-injected groups. CCs increased capillary density and preserved cardiomyocyte size in the infarcted regions suggesting CCs role in protective paracrine secretion. CONCLUSIONS: CCs merge the application of distinct cells into a single entity for cellular therapeutic intervention in the progression of heart failure. CCs are a novel cell therapy that improves on combinatorial cell approaches to support myocardial regeneration.

UCLA1, a synthetic derivative of a gp120 RNA aptamer, inhibits entry of human immunodeficiency virus type 1 subtype C.

Entry of human immunodeficiency virus type 1 (HIV-1) into cells is mediated by the virion surface envelope (Env) glycoproteins, making it a desirable target for antiretroviral entry inhibitors. We previously isolated a family of gp120 binding RNA aptamers and showed that they neutralized the infectivity of HIV-1. In this study, we assessed the activity of a shortened synthetic derivative of the B40 aptamer, called UCLA1, against a large panel of HIV-1 subtype C viruses. UCLA1 tightly bound to a consensus HIV-1 subtype C gp120 and neutralized isolates of the same subtype with 50% inhibitory concentrations (IC(50)s) in the nanomolar range. The aptamer had little toxicity in tests with cell lines and primary cells. Furthermore, it exhibited high therapeutic indices, suggesting that it may be effective at very low doses. Mapping of UCLA1 binding sites on gp120 revealed eight amino acid residues that modulated neutralization resistance. This included residues within the coreceptor binding site, at the base of the V3 loop, and in the bridging sheet within the conserved V1/V2 stem-loop of gp120. The aptamer was also shown to have synergistic effects with T20, a gp41 fusion inhibitor, and IgG1b12 (b12), an anti-CD4 binding site monoclonal antibody. These results suggest that UCLA1 may be suitable for development as a potent HIV-1 entry inhibitor.