Histological analysis of laser-enabled tissue coring with a novel 2910 nm erbium-doped fluoride glass fiber laser.

OBJECTIVES: There remains an unmet need for a laser-enabled tissue coring device that can effectively improve face and neck skin laxity and rhytides. We investigate a novel 2910 nm erbium-doped fluoride glass fiber laser (2910 nm fiber laser) (UltraClear; Acclaro Medical) for laser-coring of submental tissue. METHODS: Five subjects, Glogau scale III-IV, were treated with a single pulse of the laser-coring mode of the 2910 nm fiber laser in the submentum. A 4 mm punch biopsy was immediately performed. Biopsy specimens were sectioned and stained with hematoxylin and eosin and placed on glass slides. All sections were reviewed, and sections containing the center of the transected core were analyzed for depth and diameter of the ablative microchannel and width of the surrounding zone of coagulation. RESULTS: A total of 15 intact micro-cores were analyzed. Histological analysis revealed an average ± standard deviation microchannel diameter of 242.5 ± 65.2 µm, an average ablative depth of 980 ± 318.8 µm, and an average zone of coagulation of 104 ± 32 µm. CONCLUSIONS: Laser-enabled tissue coring with a novel 2910 nm fiber laser can safely achieve a wider microchannel diameter with ablative depth extending to the mid and deep dermis, which has the potential for collagen contraction and tissue tightening. Laser-coring to this ablation diameter and depth and with the surrounding zone of coagulation was found to be safe without adverse effects of post-inflammatory erythema or scarring in our study.

Marine predators segregate interspecifically by space and time in a sheltered coastal bay.

Marine predators are vital to the healthy functioning of coastal ecosystems, but to understand their roles, it is necessary to elucidate their movement ecology, particularly in relation to one another. A decade's worth of acoustic telemetry data (2011-2020) from Algoa Bay, South Africa, was investigated to determine how two mesopredatory species (teleosts: dusky kob Argyrosomus japonicus, n = 11, and leervis Lichia amia, n = 16) and two top predatory species (sharks: ragged-tooth sharks Carcharias taurus, n = 45, and white sharks Carcharodon carcharias, n = 31) used and shared this bay ecosystem. Multi-annual seasonal fidelity to the bay was exhibited by all species, but differences in residency were observed among species. Similarly, species used space in the bay differently-the teleosts moved less and had movements restricted to the central and western inshore regions of the bay. Conversely, the sharks roamed more, but detections were concentrated in the western part of the bay for C. taurus and in the eastern part of the bay for C. carcharias. Social network analysis showed that species segregated in space and time on a fine scale. However, there was some interaction observed between C. taurus, L. amia, and A. japonicus, but to varying degrees. This is likely because of strong habitat preferences exhibited by each species and predator-prey relationships between these predatory guilds. Results highlight that the sheltered marine Algoa Bay is a resource-rich environment, supporting multiple predators with different hunting strategies albeit similar prey preferences. Finally, these species are likely afforded some protection by the current Greater Addo Elephant National Park Marine Protected Area in the bay but are vulnerable to fishing pressure when they leave this ecosystem.

Diamond Gymnura natalensis and duckbill Aetomylaeus bovinus rays undertake nationwide coastal migrations.

Migration is a critical aspect of ocean ecosystems, and understanding this phenomenon answers ecological and management questions. Given the difficulty in tracking ocean animals across large distances, the extent to which different ray species perform long-distance movements, such as migrations, remains unknown. This study used passive acoustic telemetry to track the movements of endemic diamond Gymnura natalensis and critically endangered duckbill Aetomylaeus bovinus rays along the South African coastline using a collaborative nationwide network of coastal acoustic receivers for up to 7 years. Duckbill rays were detected significantly more frequently than diamond rays, but both species moved between the south and east coasts of South Africa (traveling up to 1167 km). Tagged individuals were detected significantly more often in their tagging locations during summer months but traveled significantly further distances during winter months. Furthermore, movement models fitted to individual duckbill rays' annual net-squared displacement identified most individual annual movements as migratory. This evidence suggests that both diamond and duckbill rays make eastward winter migrations and return to specific areas along the coastline during the summer months. The exceptions to this were diamond rays tagged on the east coast that were not found to migrate seasonally, which supports previous research that there is intraspecific variability in migrations for ray species. These findings have implications for understanding ray migration not only on a global scale but also locally for spatial management interventions and population delineation.

Full-face and neck resurfacing with a novel ablative fractional 2910 nm erbium-doped fluoride glass fiber laser for advanced photoaging.

OBJECTIVES: Ablative fractional lasers have long been considered the gold standard for facial resurfacing for advanced photoaging. These lasers offer an improved safety profile compared to traditional ablative lasers but typically require more treatment sessions given their fractional approach. In this study, we evaluate a new novel 2910 nm erbium-doped fluoride glass fiber laser (2910 nm fiber laser) (UltraClear; Acclaro Medical) for full-face and neck resurfacing for the treatment of advanced photoaging. METHODS: Twenty-two healthy subjects aged 44-80 years presenting for advanced facial photoaging and rhytides were enrolled in the study. All subjects received three full-face and neck, multipass treatments utilizing the 2910 nm fiber laser spaced 6-8 weeks apart. Subjects were asked to rate the average level of pain during the treatment. At 90 days following subjects' third treatment subjects evaluated their improvement using a Global Aesthetic Improvement Scale (GAIS) and rated their satisfaction with the treatment. Evaluation of pretreatment and posttreatment photos was completed by two blinded physician reviewers. Reviewers were asked to identify the pretreatment and posttreatment photographs and to rate the degree of improvement utilizing a GAIS. RESULTS: Fifteen participants completed the study; six were exited from the study (withdrew or lost to follow-up). The average subject GAIS score for overall appearance was 3.8. The average subject satisfaction level at follow-up was 4.8. The average subject pain score was 4.9. One blinded physician reviewer correctly identified 100% of subjects' posttreatment photographs, while the second blinded reviewer correctly identified 93%. Blinded evaluation of digital photographs revealed an average GAIS score of 3.2. Posttreatment skin responses included pin-point hemorrhage, erythema, edema, and soft tissue crusting lasting 5-7 days. There were no instances of infection, scarring or hypopigmentation. There were two instances of temporary hyperpigmentation. CONCLUSIONS: Treatment with the novel 2910 nm fiber laser is safe and effective in treating advanced photoaging and rhytides. Three treatments produced moderate to marked improvement with high patient satisfaction and treatment was associated with less discomfort and downtime compared to conventional fractional ablative lasers.

Split-face study to evaluate efficacy of global cryomodulation for reduction of pain and inflammation after nonablative fractional resurfacing.

OBJECTIVES: Cryomodulation, or the delivery of controlled cooling to downregulate inflammatory processes in the skin, has been proposed to mitigate acute side effects following various dermatologic treatments. A new controlled cooling device has been developed to deliver cryomodulation for a range of different indications. In this clinical study, we evaluate the device for the reduction of pain, erythema, and edema following nonablative fractional resurfacing (NAFR). METHODS: A single-blind, prospective, randomized, split-face study was conducted to assess the efficacy of the controlled dermal cooling device for the reduction of pain, edema, and erythema following nonablative fractional resurfacing with the dual 1550 nm erbium-doped fiber and 1927 nm thulium fiber laser. Subjects were randomized to receive a 10-min controlled cooling treatment to either the left or right side of the face immediately following full face NAFR. Pain ratings were recorded immediately postlaser treatment and immediately postcryomodulation treatment. At follow-up, subjects were surveyed for reduction of side effects and treatment satisfaction. Blinded review of photographs by two physicians was conducted to assess efficacy. RESULTS: The average pain score for subjects immediately post-NAFR was 5.15. Following cryomodulation, the average pain score on the treatment side was reduced by 69%, to an average of 1.6. The untreated side of the face was reduced by 19%, to an average of 4.2. Overall, 90% of subjects endorsed reduced discomfort. At follow-up, 70% of subjects reported a noticeable improvement in edema and 50% reported a noticeable improvement in erythema between the treatment and control sides. The average subject satisfaction score for the cryomodulation treatment was 4.2. All subjects (100%) indicated that they would elect to undergo the cryomodulation treatment again. Both blinded physician reviewers were successful in identifying the cryomodulation-treated side of the face in 70% of subjects' posttreatment photographs. CONCLUSIONS: The results of this split-face study support the efficacy of a global cryomodulation device for the reduction of pain, edema, and erythema following NAFR treatment. Cryomodulation was delivered in a simple 10 min procedure and yielded high patient satisfaction.

The fate and movements of aquarium-released giant trevally Caranx ignobilis inferred from acoustic telemetry.

Movements of four adult giant trevally Caranx ignobilis were tracked using passive acoustic telemetry after being released from uShaka Sea World Aquarium in Durban, South Africa, where they had been kept on display for a period of 8 years. All four individuals were detected on a large network of deployed acoustic receivers for a minimum of 3 months to a maximum of over 6 years. Their movements were compared to 43 wild-caught and tagged C. ignobilis over a similar period and two individuals adopted movement behavior similar to that of their conspecifics, including repeated annual seasonal migrations to a known spawning aggregation site. This study shows that with good animal husbandry, indigenous fish kept in captivity can be released back into the wild and not only survive but adopt natural movement behavior and contribute to future generations of their species.

Microglia secrete distinct sets of neurotoxins in a stimulus-dependent manner.

Microglia are the resident immune cells of the brain which regulate both the innate and adaptive neuroimmune responses in health and disease. In response to specific endogenous and exogenous stimuli, microglia transition to one of their reactive states characterized by altered morphology and function, including their secretory profile. A component of the microglial secretome is cytotoxic molecules capable of causing damage and death to nearby host cells, thus contributing to the pathogenesis of neurodegenerative disorders. Indirect evidence from secretome studies and measurements of mRNA expression using diverse microglial cell types suggest different stimuli may induce microglia to secrete distinct subsets of cytotoxins. We demonstrate the accuracy of this hypothesis directly by challenging murine BV-2 microglia-like cells with eight different immune stimuli and assessing secretion of four potentially cytotoxic molecules, including nitric oxide (NO), tumor necrosis factor α (TNF), C-X-C motif chemokine ligand 10 (CXCL10), and glutamate. Lipopolysaccharide (LPS) and a combination of interferon (IFN)-γ plus LPS induced secretion of all toxins studied. IFN-ß, IFN-γ, polyinosinic:polycytidylic acid (poly I:C), and zymosan A upregulated secretion of subsets of these four cytotoxins. LPS and IFN-γ, alone or in combination, as well as IFN-ß induced toxicity of BV-2 cells towards murine NSC-34 neuronal cells, while ATP, N-formylmethionine-leucyl-phenylalanine (fMLP), and phorbol 12-myristate 13-acetate (PMA) did not affect any parameters studied. Our observations contribute to a growing body of knowledge on the regulation of the microglial secretome, which may inform future development of novel therapeutics for neurodegenerative diseases, where dysregulated microglia are key contributors to pathogenesis.

Cardiolipin released by microglia can act on neighboring glial cells to facilitate the uptake of amyloid-ß (1-42).

Cardiolipin is a mitochondrial phospholipid that is also detected in serum inferring its extracellular release; however, this process has not been directly demonstrated for any of the brain cell types. Nevertheless, extracellular cardiolipin has been shown to modulate several neuroimmune functions of microglia and astrocytes, including upregulation of their endocytic activity. Low cardiolipin levels are associated with brain aging, and may thus hinder uptake of amyloid-ß (Αß) in Alzheimer's disease. We hypothesized that glial cells are one of the sources of extracellular cardiolipin in the brain parenchyma where this phospholipid interacts with neighboring cells to upregulate the endocytosis of Αß. Liquid chromatography-mass spectrophotometry identified 31 different species of cardiolipin released from murine BV-2 microglial cells and revealed this process was accelerated by exposure to Aß42. Extracellular cardiolipin upregulated internalization of fluorescently-labeled Aß42 by primary murine astrocytes, human U118 MG astrocytic cells, and murine BV-2 microglia. Increased endocytic activity in the presence of extracellular cardiolipin was also demonstrated by studying uptake of Aß42 and pHrodo™ Bioparticles™ by human induced pluripotent stem cells (iPSCs)-derived microglia, as well as iPSC-derived human brain organoids containing microglia, astrocytes, oligodendrocytes and neurons. Our observations indicate that Aß42 augments the release of cardiolipin from microglia into the extracellular space, where it can act on microglia and astrocytes to enhance their endocytosis of Aß42. Our observations suggest that the reduced glial uptake of Aß due to the decreased levels of cardiolipin could be at least partially responsible for the extracellular accumulation of Aß in aging and Alzheimer's disease.

#CoreCosmeticSpecialties: An analysis of nonsurgical cosmetic procedure hashtags on Instagram.

OBJECTIVES: In this study, we seek to characterize both the account credentials and content type for posts among the most popular nonsurgical cosmetic procedure hashtags on Instagram. METHODS: Twenty-five hashtags related to nonsurgical cosmetic procedures were identified with over 250,000 posts each, ranging from 256,000 to 12.1 million posts per hashtag. The first 10 posts displayed under the "Top" section for each hashtag within Instagram, as sorted by Instagram's proprietary algorithm, were analyzed for account type and content type. Posts unrelated to the cosmetic procedure or with non-English captions were excluded. In total, 680 posts were queried with 250 posts meeting the inclusion criteria. RESULTS: Content creators included nonphysician providers (68%), core cosmetic physicians (12%), noncore cosmetic physicians (8%), and consumers or others (13%). Content type included before and after (45%), self-promotional (23%), educational (17%), personal (5%), entertainment (5%), and promotional (5%). Among the different content creator types, core cosmetic physicians had the largest proportion of educational content at 38%. CONCLUSIONS: High-quality educational content on Instagram from core cosmetic specialties is scarce. By increasing their presence on Instagram, core cosmetic physicians can provide patient education, counteract misinformation, and raise awareness on training and qualifications regarding nonsurgical cosmetic procedures.

Potential neurotoxic activity of diverse molecules released by astrocytes.

Astrocytes are the main support cells of the central nervous system. They also participate in neuroimmune reactions. In response to pathological and immune stimuli, astrocytes transform to reactive states characterized by increased release of inflammatory mediators. Some of these molecules are neuroprotective and inflammation resolving while others, including reactive oxygen species (ROS), nitric oxide (NO), matrix metalloproteinase (MMP)- 9, L-glutamate, and tumor necrosis factor α (TNF), are well-established toxins known to cause damage to surrounding cells and tissues. We hypothesized that similar to microglia, the brain immune cells, reactive astrocytes can release a broader set of diverse molecules that are potentially neurotoxic. A literature search was conducted to identify such molecules using the following two criteria: 1) evidence of their expression and secretion by astrocytes and 2) direct neurotoxic action. This review describes 14 structurally diverse molecules as less-established astrocyte neurotoxins, including C-X-C motif chemokine ligand (CXCL)10, CXCL12/CXCL12(5-67), FS-7-associated surface antigen ligand (FasL), macrophage inflammatory protein (MIP)- 2α, TNF-related apoptosis inducing ligand (TRAIL), pro-nerve growth factor (proNGF), pro-brain-derived neurotrophic factor (proBDNF), chondroitin sulfate proteoglycans (CSPGs), cathepsin (Cat)B, group IIA secretory phospholipase A2 (sPLA2-IIA), amyloid beta peptides (Aß), high mobility group box (HMGB)1, ceramides, and lipocalin (LCN)2. For some of these molecules, further studies are required to establish either their direct neurotoxic effects or the full spectrum of stimuli that induce their release by astrocytes. Only limited studies with human-derived astrocytes and neurons are available for most of these potential neurotoxins, which is a knowledge gap that should be addressed in the future. We also summarize available evidence of the role these molecules play in select neuropathologies where reactive astrocytes are a key feature. A comprehensive understanding of the full spectrum of neurotoxins released by reactive astrocytes is key to understanding neuroinflammatory diseases characterized by the adverse activation of these cells and may guide the development of novel treatment strategies.

Useful cytological confirmation of HPV 13 in lesional mucosa enhances diagnosis of focal epithelial hyperplasia.

An 11-year-old female presented with multiple oral lesions for several months. Histopathological findings suggested focal epithelial hyperplasia (FEH), also known as Heck disease. FEH is strongly associated with Human papillomavirus (HPV), especially genotypes 13 and 32. An oral swab of a mucosal lesion was subsequently obtained for cytology, immunohistochemistry and in situ hybridization. In addition, in situ hybridization and immunohistochemistry were also performed retrospectively on the biopsy specimen for correlation. The cytology specimen showed squamous cells with enlarged, slightly atypical nuclei and rare perinuclear halos. The histology findings included papillomatosis with acanthosis, mild nuclear atypia and focal perinuclear halos. The immunohistochemistry for the consensus HPV L1 capsid protein was found in both the cytology and biopsy specimens indicating that the lesion was HPV-related. High viral copy numbers of HPV 13 were detected by in situ hybridization in both the cytology and histology specimens. Although histologic features of FEH have been well characterized in the literature, to our knowledge, this is the first case to describe in FEH with adjunct immunohistochemistry and in situ hybridization results. Furthermore, these findings assisted in our diagnosis since the patient's clinical presentation was a diagnostic challenge with smooth dome-shaped papules instead of the typically described flat-topped verrucous lesions seen in FEH. In summary, our case reveals that there is a high concordance between the HPV 13 detection in the cytology and histology of FEH, and that performing cytology in addition to histology can be used to optimize diagnostic evaluation towards appropriate patient care.

Extracellular Cardiolipin Modulates Select Immune Functions of Astrocytes in Toll-Like Receptor (TLR) 4-Dependent Manner.

Alzheimer's disease (AD) is characterized by chronic neuroinflammation, which is partially mediated by dysregulated functions of glial cells. Cardiolipin (CL) is a phospholipid normally confined to the inner mitochondrial membrane; however, it has been detected in human sera, indicating that it can exist in the extracellular space where it may interact with nearby cells. Although CL has been shown to modulate several functions of microglia in a toll-like receptor (TLR) 4-dependent manner, the effects of extracellular CL on astrocytes are unknown. In addition to their homeostatic functions, astrocytes participate in neuroimmune responses of the brain and express TLR 4. Therefore, we hypothesized that extracellular CL (1) modulates the secretion of cytokines and cytotoxins by astrocytes, as well as their phagocytic activity, and (2) acts by interacting with astrocyte TLR 4. We demonstrate that CL inhibits the lipopolysaccharide- (LPS-) induced secretion of cytotoxins and expression of glial fibrillary acidic protein (GFAP) by human U118 MG astrocytic cells. CL alone upregulates the phagocytic activity of human astrocytic cells and primary murine astrocytes. CL in combination with LPS upregulates secretion of interleukin (IL)-1ß by astrocytic cells. Furthermore, CL alone increases the secretion of monocyte chemoattractant protein (MCP)-1 by astrocytic cells, which is blocked by the TLR 4-specific antagonist TAK-242. We demonstrate that CL upregulates MCP-1 secretion in the absence of its natural carrier protein, ß2-glycoprotein 1, indicating that CL may be bioactive in the brain where this protein is not present. Lastly, we show that CL downregulates the expression of astrocytic TLR 4, implying that CL engages this receptor, as its activation has been shown to lead to its degradation. Overall, our study extends the list of cell type functions of which CL modulates and provides evidence that CL, or liposomes containing this phospholipid can be used to modulate specific neuroimmune functions of astrocytes.