Framboesiform Facial Lesions and Chorioretinopathy as Presenting Signs of Syphilis in an Immunocompetent Patient.

ABSTRACT: Syphilis has long been considered the "great masquerader," notorious for its varying presentations and ability to affect most organ systems in the body. We report the case of a 41-year-old immunocompetent man who presented to ophthalmology with rapidly progressive visual complaints from bilateral panuveitis and concomitant verrucous facial lesions initially disregarded by the patient as acne. Serum testing for syphilis was positive, and he was admitted for 14 days of intravenous (IV) penicillin with multiservice care from dermatology, ophthalmology, and infectious disease. We present photographic documentation showing his stepwise resolution of his facial and retinal involvement with penicillin treatment course. This case is unusual in the concomitant presentation of ocular and facial syphilitic findings in an immunocompetent patient and highlights the need to include syphilis in the differential for unusual appearances.

Chronic Purulent Conjunctivitis Associated With Extensively Drug-Resistant Pseudomonas aeruginosa.

This case report describes a patient with a chronic urinary tract infection whose long-term treatment for right eye redness, discharge, pain, and decreased vision ultimately led to hospitalization and Pseudomonas aeruginosa resistant to multiple antibiotics.

Bilateral zonular dehiscence during cataract surgery in a patient with systemic sclerosis.

Purpose: Systemic sclerosis, also known as scleroderma, is a rare and chronic autoimmune connective disorder that affects most organs. While clinical findings of scleroderma patients in the context of the eye have been described to include lid fibrosis and glaucoma, almost nothing has been reported regarding ophthalmologic surgical complications in scleroderma patients. Observations: Here, we report bilateral zonular dehiscence and iris prolapse during two independent cataract extractions performed by separate experienced anterior segment surgeons in a patient with known systemic sclerosis. The patient did not have any other known risk factors for these complications to occur. Conclusions and Importance: In our patient, bilateral zonular dehiscence raised the possibility of poor connective tissue support secondary to scleroderma. We recommend that clinicians are aware of potential complications in performing anterior segment surgery in patients with known or suspected scleroderma.

Dioleoylphosphatidylglycerol Inhibits Heat Shock Protein B4 (HSPB4)-Induced Inflammatory Pathways In Vitro.

Our previous work shows that dioleoylphosphatidylglycerol (DOPG) accelerates corneal epithelial healing in vitro and in vivo by unknown mechanisms. Prior data demonstrate that DOPG inhibits toll-like receptor (TLR) activation and inflammation induced by microbial components (pathogen-associated molecular patterns, PAMPs) and by endogenous molecules upregulated in psoriatic skin, which act as danger-associated molecular patterns (DAMPs) to activate TLRs and promote inflammation. In the injured cornea, sterile inflammation can result from the release of the DAMP molecule, heat shock protein B4 (HSPB4), to contribute to delayed wound healing. Here, we show in vitro that DOPG inhibits TLR2 activation induced in response to HSPB4, as well as DAMPs that are elevated in diabetes, a disease that also slows corneal wound healing. Further, we show that the co-receptor, cluster of differentiation-14 (CD14), is necessary for PAMP/DAMP-induced activation of TLR2, as well as of TLR4. Finally, we simulated the high-glucose environment of diabetes to show that elevated glucose levels enhance TLR4 activation by a DAMP known to be upregulated in diabetes. Together, our results demonstrate the anti-inflammatory actions of DOPG and support further investigation into its development as a possible therapy for corneal injury, especially in diabetic patients at high risk of vision-threatening complications.

Developmental plasticity of epithelial stem cells in tooth and taste bud renewal.

In Lake Malawi cichlids, each tooth is replaced in one-for-one fashion every ∼20 to 50 d, and taste buds (TBs) are continuously renewed as in mammals. These structures are colocalized in the fish mouth and throat, from the point of initiation through adulthood. Here, we found that replacement teeth (RT) share a continuous band of epithelium with adjacent TBs and that both organs coexpress stem cell factors in subsets of label-retaining cells. We used RNA-seq to characterize transcriptomes of RT germs and TB-bearing oral epithelium. Analysis revealed differential usage of developmental pathways in RT compared to TB oral epithelia, as well as a repertoire of genome paralogues expressed complimentarily in each organ. Notably, BMP ligands were expressed in RT but excluded from TBs. Morphant fishes bathed in a BMP chemical antagonist exhibited RT with abrogated shh expression in the inner dental epithelium (IDE) and ectopic expression of calb2 (a TB marker) in these very cells. In the mouse, teeth are located on the jaw margin while TBs and other oral papillae are located on the tongue. Previous study reported that tongue intermolar eminence (IE) oral papillae of Follistatin (a BMP antagonist) mouse mutants exhibited dysmorphic invagination. We used these mutants to demonstrate altered transcriptomes and ectopic expression of dental markers in tongue IE. Our results suggest that vertebrate oral epithelium retains inherent plasticity to form tooth and taste-like cell types, mediated by BMP specification of progenitor cells. These findings indicate underappreciated epithelial cell populations with promising potential in bioengineering and dental therapeutics.

A quiescent cell population replenishes mesenchymal stem cells to drive accelerated growth in mouse incisors.

The extent to which heterogeneity within mesenchymal stem cell (MSC) populations is related to function is not understood. Using the archetypal MSC in vitro surface marker, CD90/Thy1, here we show that 30% of the MSCs in the continuously growing mouse incisor express CD90/Thy1 and these cells give rise to 30% of the differentiated cell progeny during postnatal development. In adulthood, when growth rate homeostasis is established, the CD90/Thy1+ MSCs decrease dramatically in number. When adult incisors are cut, the growth rate increases to rapidly re-establish tooth length and homeostasis. This accelerated growth rate correlates with the re-appearance of CD90/Thy+ MSCs and re-establishment of their contribution to cell differentiation. A population of Celsr1+ quiescent cells becomes mitotic following clipping and replenishes the CD90/Thy1 population. A sub-population of MSCs thus exists in the mouse incisor, distinguished by expression of CD90/Thy1 that plays a specific role only during periods of increased growth rate.

Developmental Plasticity of Patterned and Regenerating Oral Organs.

In many aquatic vertebrates, including bony and cartilaginous fishes, teeth and taste buds colocalize on jaw elements. In these animals, taste buds are renewed continuously throughout life, whereas teeth undergo cycled whole-organ replacement by various means. Recently, studies of cichlid fishes have yielded new insights into the development and regeneration of these dental and sensory oral organs. Tooth and taste bud densities covary positively across species with different feeding strategies, controlled by common regions of the genome and integrated molecular signals. Developing teeth and taste buds share a bipotent epithelium during early patterning stages, from which dental and taste fields are specified. Moreover, these organs share a common epithelial ribbon that supports label-retaining cells during later stages of regeneration. During both patterning and regeneration stages, dental organs can be converted to taste bud fate by manipulation of BMP signaling. These observations highlight a surprising long-term plasticity between dental and sensory organ types. Here, we review these findings and discuss the implications of developmental plasticity that spans the continuum of craniofacial organ patterning and regeneration.

Coevolutionary patterning of teeth and taste buds.

Teeth and taste buds are iteratively patterned structures that line the oro-pharynx of vertebrates. Biologists do not fully understand how teeth and taste buds develop from undifferentiated epithelium or how variation in organ density is regulated. These organs are typically studied independently because of their separate anatomical location in mammals: teeth on the jaw margin and taste buds on the tongue. However, in many aquatic animals like bony fishes, teeth and taste buds are colocalized one next to the other. Using genetic mapping in cichlid fishes, we identified shared loci controlling a positive correlation between tooth and taste bud densities. Genome intervals contained candidate genes expressed in tooth and taste bud fields. sfrp5 and bmper, notable for roles in Wingless (Wnt) and bone morphogenetic protein (BMP) signaling, were differentially expressed across cichlid species with divergent tooth and taste bud density, and were expressed in the development of both organs in mice. Synexpression analysis and chemical manipulation of Wnt, BMP, and Hedgehog (Hh) pathways suggest that a common cichlid oral lamina is competent to form teeth or taste buds. Wnt signaling couples tooth and taste bud density and BMP and Hh mediate distinct organ identity. Synthesizing data from fish and mouse, we suggest that the Wnt-BMP-Hh regulatory hierarchy that configures teeth and taste buds on mammalian jaws and tongues may be an evolutionary remnant inherited from ancestors wherein these organs were copatterned from common epithelium.