Spatial Transcriptomics Suggests That Alterations Occur in the Preneoplastic Breast Microenvironment of BRCA1/2 Mutation Carriers.

Breast cancer is the most common cancer in females, affecting one in every eight women and accounting for the majority of cancer-related deaths in women worldwide. Germline mutations in the BRCA1 and BRCA2 genes are significant risk factors for specific subtypes of breast cancer. BRCA1 mutations are associated with basal-like breast cancers, whereas BRCA2 mutations are associated with luminal-like disease. Defects in mammary epithelial cell differentiation have been previously recognized in germline BRCA1/2 mutation carriers even before cancer incidence. However, the underlying mechanism is largely unknown. Here, we employ spatial transcriptomics to investigate defects in mammary epithelial cell differentiation accompanied by distinct microenvironmental alterations in preneoplastic breast tissues from BRCA1/2 mutation carriers and normal breast tissues from noncarrier controls. We uncovered spatially defined receptor-ligand interactions in these tissues for the investigation of autocrine and paracrine signaling. We discovered that ß1-integrin-mediated autocrine signaling in BRCA2-deficient mammary epithelial cells may differ from BRCA1-deficient mammary epithelial cells. In addition, we found that the epithelial-to-stromal paracrine signaling in the breast tissues of BRCA1/2 mutation carriers is greater than in control tissues. More integrin-ligand pairs were differentially correlated in BRCA1/2-mutant breast tissues than noncarrier breast tissues with more integrin receptor-expressing stromal cells. IMPLICATIONS: These results suggest alterations in the communication between mammary epithelial cells and the microenvironment in BRCA1 and BRCA2 mutation carriers, laying the foundation for designing innovative breast cancer chemo-prevention strategies for high-risk patients.

Alterations in the preneoplastic breast microenvironment of BRCA1/2 mutation carriers revealed by spatial transcriptomics.

Breast cancer is the most common cancer in females, affecting one in every eight women and accounting for the majority of cancer-related deaths in women worldwide. Germline mutations in the BRCA1 and BRCA2 genes are significant risk factors for specific subtypes of breast cancer. BRCA1 mutations are associated with basal-like breast cancers, whereas BRCA2 mutations are associated with luminal-like disease. There are currently few chemoprevention strategies available for BRCA1/2 mutation carriers, and irreversible prophylactic mastectomy is the primary option. Designing chemo-preventive strategies requires an in-depth understanding of the physiological processes underlying tumor initiation. Here, we employ spatial transcriptomics to investigate defects in mammary epithelial cell differentiation accompanied by distinct microenvironmental alterations in preneoplastic breast tissues from BRCA1/2 mutation carriers and normal breast tissues from non-carrier controls. We uncovered spatially defined receptor-ligand interactions in these tissues for the investigation of autocrine and paracrine signaling. We discovered that ß1-integrin-mediated autocrine signaling in BRCA2-deficient mammary epithelial cells differs from BRCA1-deficient mammary epithelial cells. In addition, we found that the epithelial-to-stromal paracrine signaling in the breast tissues of BRCA1/2 mutation carriers is greater than in control tissues. More integrin-ligand pairs were differentially correlated in BRCA1/2-mutant breast tissues than non-carrier breast tissues with more integrin receptor-expressing stromal cells. These results reveal alterations in the communication between mammary epithelial cells and the microenvironment in BRCA1 and BRCA2 mutation carriers, laying the foundation for designing innovative breast cancer chemo-prevention strategies for high-risk patients.

Capsular tension ring in the management of occult lens zonular dehiscence in infantile glaucoma.

The authors present a case of bilateral zonular dehiscence in a boy with infantile glaucoma who had developed cataracts. The zonular dehiscence was noted at the beginning of cataract surgery. The cataracts were removed and capsular tension rings and intraocular lenses were safely inserted and remained well centered.

Diplopia and strabismus following ocular surgeries.

Postoperative diplopia and strabismus may result from a variety of ocular surgical procedures. Common underlying mechanisms include sensory disturbance, scarring, direct extraocular muscle injury, myotoxicity from injections of local anesthesia or antibiotics, and malpositioning of extraocular muscles by implant materials. The most common patterns are vertical and horizontal motility disturbance. Treatment options include prisms, botulinum, occlusion, or surgery.

Cut and paste: sutureless conjunctival closure in strabismus surgery.

PURPOSE: This study investigated the use of fibrin glue and compared its effect with traditional sutures for conjunctival closure in strabismus surgery. METHODS: The study included 12 patients undergoing horizontal strabismus surgery, of whom 5 underwent bilateral medial rectus muscle recessions and 7 underwent bilateral lateral rectus muscle recessions. For each patient, fibrin glue was used to close the conjunctiva of one eye and 6-0 plain sutures were used to close the other. RESULTS: All eyes maintained adequate closure of the conjunctiva postoperatively and there were no intraoperative or postoperative complications for an eye. However, the average surgical time needed to apply fibrin glue was considerable less than that required for closure with sutures. Furthermore, eyes closed with fibrin glue were associated with significantly less postoperative inflammation and patient discomfort than those closed with sutures. All patients and parents reported significantly less discomfort from the eyes treated with fibrin glue. CONCLUSION: These results are promising and demonstrated a safe and effective alternative to traditional suture closure in strabismus surgery. When compared to traditional suture closure, conjunctival closure with glue includes the following advantages: less postoperative patient discomfort, diminished postoperative inflammation, and potentially reduced surgical time with corresponding reduced time under general anesthesia.

Special Care Dentistry Association consensus statement on sedation, anesthesia, and alternative techniques for people with special needs.

Many people with special needs (PSN) have difficulty having good oral health or accessing oral health services because of a disability or medical condition. The number of people with these conditions living in community settings and needing oral health services is increasing dramatically due to advances in medical care, deinstitutionalization, and changing societal values. Many of these individuals require additional supports beyond local anesthesia in order to receive dental treatment services. The purpose of this consensus statement is to focus on the decision-making process for choosing a method of treatment or a combination of methods for facilitating dental treatment for these individuals. These guidelines are intended to assist oral health professionals and other interested parties in planning and carrying out oral health treatment for PSN. Considerations for planning treatment and considerations for each of several alternative modalities are listed. Also discussed are considerations for the use of combinations of modalities and considerations for the repeated or frequent use of these modalities. Finally, the need to advocate for adequate education and reimbursement for the full range of support alternatives is addressed. The Special Care Dentistry Association (SCDA) is dedicated to improving oral health and well being of PSN. The SCDA hopes that these guidelines can help oral health professionals and other interested individuals and groups to work together to ensure that PSN can achieve a "lifetime of oral health."

Providing deep sedation and general anesthesia for patients with special needs in the dental office-based setting.

This article discusses the issues of morbidity and mortality associated with deep sedation and general anesthesia specifically in the dental office-based setting for patients with special needs (PSN). A focused review of a particular environment and patient population was challenging as it was difficult to identify articles that discuss the unique scope of this subject. During the review of the literature, no article was identified that discussed this exact topic. There were articles that discussed the delivery of general anesthesia for PSN in an outpatient setting and associated issues of morbidity and mortality. There were also articles and sources of information that discussed the delivery of general anesthesia for other patient populations in the office-based setting. In an effort to support the scope of this article, some of these articles are discussed as they pertain to the subject of this article. In addition, an analysis of the author's practice over a 4-year period is discussed in an effort to present relevant data per the scope of this article. After reviewing the literature and the author's clinical practice, it appears that the incidence of mortality for PSN in the dental office-based setting is minimal and the incidence of morbidity for this same population is limited to relatively minor events. Ultimately, it was concluded that the delivery of general anesthesia for PSN in the dental office-based setting can be considered a very safe and successful procedure.

Lymphangioma of the conjunctiva and nasal cavity in a child presenting with diffuse subconjunctival hemorrhage and nosebleeds.

A 4-year-old girl had extensive subconjunctival hemorrhage in the right eye. She had recurrent minor nosebleeds starting at 6 months. Visual acuity was 20/20. Anterior segment examination showed diffuse, blood-filled, multilobulated cystic channels in the conjunctiva. Bleeding resolved, leaving transparent cystic channels. Conjunctival lymphangioma can manifest as temporary subconjunctival lymphangioma.

A comparison of the effectiveness of four biostains in enhancing visualization of the vitreous.

PURPOSE: To compare the effectiveness of four biostains in vitreous staining as a means to facilitate clean anterior vitrectomy. MATERIALS AND METHODS: Four biostains (fluorescein, indocyanine green, trypan blue, and triamcinolone acetonide) were used to stain the transparent vitreous of human cadaver and monkey cadaver eyes. Results were compared and recorded by digital photography and videography. RESULTS: Of the four biostains, triamcinolone acetonide best highlighted the vitreous. Although fluorescein, indocyanine green, and trypan blue also produced acceptable vitreous staining, the surrounding ocular structures were slightly stained as well. CONCLUSION: All four biostains enhanced visualization of the vitreous. However, triamcinolone acetonide best highlighted the vitreous.

Management of the anterior and posterior lens capsules and vitreous in pediatric cataract surgery.

PURPOSE: To review and discuss the advantages and disadvantages of various methods of managing anterior and posterior lens capsules and anterior vitreous in pediatric cataract surgery. METHODS: We reviewed the literature related to pediatric cataract surgery on PubMed and subclassified the subject into subtopics for managing the anterior lens capsule, posterior lens capsule, and anterior vitreous. RESULTS: After a review of the literature, we summarized the advantages and disadvantages of various approaches related to surgical managements of the anterior lens capsule, posterior lens capsule, and anterior vitreous in pediatric cataract surgery. We discussed recommendations from the literature and commented on our experiences related to the above subtopics. CONCLUSION: In the surgical management of pediatric cataract, anterior continuous curvilinear capsulorhexis provides the most reliable and tear-resistant capsular opening. Vitrectorhexis and radiofrequency diathermy, on the other hand, are alternative approaches (depending on the surgeon's personal preference). Primary posterior continuous curvilinear capsulorhexis may delay the onset of posterior capsule opacification. Anterior vitrectomy may be necessary to prevent or eliminate the onset of posterior capsule opacification in young children.

Enhanced visualization of capsulorhexis with indocyanine green staining in pediatric white cataracts.

PURPOSE: To evaluate the enhancement of the visualization of the anterior lens capsule with indocyanine green (ICG) in pediatric dense, mature cataracts. PATIENTS AND METHODS: Six children (10 eyes) 4 to 9 years old with complete, white cataracts underwent ICG-enhanced cataract surgery. RESULTS: All of the eyes showed a complete continuous curvilinear capsulorhexis and a well-centered intracapsular implant. No surgical or postoperative complications were encountered. CONCLUSION: Staining the anterior capsule with ICG is an excellent way to facilitate performance of an anterior capsulorhexis in pediatric white cataracts.