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.

Pathogenesis-directed treatment of linear porokeratosis with topical cholesterol-lovastatin.

A 2-year-old boy presented with an extensive, asymptomatic, photosensitive eruption refractory to topical steroids and tretinoin; examination and biopsies were consistent with generalized linear porokeratosis involving the face, limbs, and trunk. Treatment with topical cholesterol-lovastatin was initiated, and it successfully improved early erythematous lesions. Whole exome sequencing that targeted mevalonate pathway genes crucial in cholesterol synthesis later revealed a pathogenic, paternally inherited, porokeratosis-associated MVD, c.70+5 G>A, mutation. Topical cholesterol-lovastatin is a safe and effective empiric treatment for porokeratosis when used in the early, erythematous phase, and its success is likely mediated through its role in targeting mevalonate pathway mutations.

Clinical evaluation of a new fractional ablative 2910 nm erbium laser on photodamaged skin: A pilot study.

OBJECTIVE: To examine the efficacy and safety of a new fractional, ablative erbium:glass fiber (Er:glass) laser (2910 nm) at improving clinical signs of photodamaged skin. MATERIALS AND METHODS: Thirty-seven healthy participants aged 38-75 years with photodamaged skin were enrolled into two treatment groups. Group A (n = 14) received up to four laser treatments with mild settings, and focal facial subunits were treated with deeper settings. Group B (n = 23) received a single treatment using deeper settings. Following treatment, pain scores and severity and duration of skin responses (erythema, edema, and pinpoint bleeding) were assessed. Primary outcome was the improvement in participant and investigator Global Aesthetic Improvement Scale (GAIS) at 3-month follow-up. Secondary outcomes were participant satisfaction with treatment and whether they would repeat treatment. RESULTS: Thirty-five participants completed the study (n = 1 lost to follow up in each group). Both groups had similar mean participant and investigator GAIS scores of 3/5 corresponding to "Improvement." All but two patients (both from Group A) reported improvement, satisfaction with treatment, and would repeat treatment. Posttreatment skin responses were mild-to-moderate, lasting up to 5 days. There was no scarring or dyspigmentation. CONCLUSION: The 2910 nm Er:glass laser provided improvement in photoaging with high patient satisfaction.

Better Understanding the Disparity Associated With Black Race in Heart Transplant Outcomes: A National Registry Analysis.

BACKGROUND: Black heart transplant recipients have higher risk of mortality than White recipients. Better understanding of this disparity, including subgroups most affected and timing of the highest risk, is necessary to improve care of Black recipients. We hypothesize that this disparity may be most pronounced among young recipients, as barriers to care like socioeconomic factors may be particularly salient in a younger population and lead to higher early risk of mortality. METHODS: We studied 22 997 adult heart transplant recipients using the Scientific Registry of Transplant Recipients data from January 2005 to 2017 using Cox regression models adjusted for recipient, donor, and transplant characteristics. RESULTS: Among recipients aged 18 to 30 years, Black recipients had 2.05-fold (95% CI, 1.67-2.51) higher risk of mortality compared with non-Black recipients (P<0.001, interaction P<0.001); however, the risk was significant only in the first year post-transplant (first year: adjusted hazard ratio, 2.30 [95% CI, 1.60-3.31], P<0.001; after first year: adjusted hazard ratio, 0.84 [95% CI, 0.54-1.29]; P=0.4). This association was attenuated among recipients aged 31 to 40 and 41 to 60 years, in whom Black recipients had 1.53-fold ([95% CI, 1.25-1.89] P<0.001) and 1.20-fold ([95% CI, 1.09-1.33] P<0.001) higher risk of mortality. Among recipients aged 61 to 80 years, no significant association was seen with Black race (adjusted hazard ratio, 1.12 [95% CI, 0.97-1.29]; P=0.1). CONCLUSIONS: Young Black recipients have a high risk of mortality in the first year after heart transplant, which has been masked in decades of research looking at disparities in aggregate. To reduce overall racial disparities, clinical research moving forward should focus on targeted interventions for young Black recipients during this period.

Disseminated Eruptive Blue Nevi in a Young Adult Patient.

Common blue nevi tend to be singular or localized, with multiple eruptive blue nevi being a rare occurrence. We report the case of a young adult who presented with multiple asymptomatic lesions that had appeared gradually over a few years. Physical examination revealed 30 distinct, blue-gray macules diffusely over the medial buttocks, lower back, and dorsal arms. Histopathology showed pigmented dendritic melanocytes with associated melanophages, features characteristic of blue nevus. This case demonstrates that eruptive blue nevi can present as numerous, disseminated lesions over multiple anatomic sites. Recognition of the various patterns of eruptive blue nevi and their benign nature can reduce unnecessary biopsies and work-up.

Cut-off levels for hyperandrogenemia among Samoan women: An improved methodology for deriving normative data in an obese population.

OBJECTIVE: To define biochemical hyperandrogenemia (HA) among a population-based sample of reproductive-aged Samoan women, taking into consideration their high BMI levels. DESIGN AND METHODS: A secondary analysis was performed among a cross-sectional sample of Samoan women aged 25-39years (n=494) who were part of a larger genome-wide association study (GWAS) of adiposity. Women indicating pregnancy/lactation, hysterectomy, oophorectomy, cancer treatment, or use of contraceptive injections were excluded from the study. We analyzed the distribution of free androgen index (FAI) values to establish normative androgen data among Samoan women of reproductive age. Using the lowest tertile of body mass index (BMI), we defined HA as free androgen index (FAI) values >95(th) FAI percentile in that subsample. We compared the anthropometric and metabolic characteristics of women with HA to women with normal androgen levels. RESULTS: HA was defined as FAI>8.5. Using this definition, 14% of women were classified as hyperandrogenemic. Women with HA had significantly higher average BMI values, abdominal circumferences, fasting triglycerides, and insulin levels as well as significantly lower adiponectin levels. CONCLUSION: This study is the first to define normative androgen values among Samoan women with a quantitative assessment of the relationship between adiposity and androgen levels. The uniquely high BMI levels in the population not only provide important clinical insight into normative androgen values among Samoan women, but they also serve as references for the clinical assessment of HA, taking into consideration BMI, in other populations.

Placenta-secreted circulating markers in pregnant women with obstructive sleep apnea.

AIMS: Obstructive sleep apnea (OSA) is associated with placenta-mediated adverse clinical outcomes. We aimed at comparing placenta-secreted proteins, such as first and second trimester Down syndrome screening markers which have been linked to preeclampsia, and markers of angiogenesis in pregnant women with OSA, and pregnant controls at low risk for OSA. METHODS: A case-control study of pregnant women with OSA and controls at low risk for OSA was performed. Levels of first and second trimester markers were reported as multiple of median (MoM), and adjusted for body mass index (BMI). Stored samples were tested for markers of angiogenesis and adjusted for gestational age, BMI, and chronic hypertension. RESULTS: A total of 24 women with OSA and 166 controls had screening markers. BMI was higher in cases compared to controls, P=0.01. MoM levels of placenta associated plasma protein-A (PAPP-A) were significantly lower in cases versus controls, even after adjusting for BMI (0.52 IQR 0.48 vs. 1.01 IQR 0.63, P=0.009). The ratio of soluble vascular endothelial growth factor receptor 1 to placental growth factor was significantly higher in cases than controls, even after adjusting for confounders (4.42 IQR 2.52 vs. 2.93 IQR 2.01, P=0.009). CONCLUSION: Circulating placenta-secreted glycoproteins and markers of angiogenesis are altered in pregnant women with OSA.

Community-based interventions for the prevention and control of helmintic neglected tropical diseases.

In this paper, we aim to systematically analyze the effectiveness of community-based interventions (CBIs) for the prevention and control of helminthiasis including soil-transmitted helminthiasis (STH) (ascariasis, hookworms, and trichuriasis), lymphatic filariasis, onchocerciasis, dracunculiasis, and schistosomiasis. We systematically reviewed literature published before May 2013 and included 32 studies in this review. Findings from the meta-analysis suggest that CBIs are effective in reducing the prevalence of STH (RR: 0.45, 95% CI: 0.38, 0.54), schistosomiasis (RR: 0.40, 95% CI: 0.33, 0.50), and STH intensity (SMD: -3.16, 95 CI: -4.28, -2.04). They are also effective in improving mean hemoglobin (SMD: 0.34, 95% CI: 0.20, 0.47) and reducing anemia prevalence (RR: 0.90, 95% CI: 0.85, 0.96). However, it did not have any impact on ferritin, height, weight, low birth weight (LBW), or stillbirths. School-based delivery significantly reduced STH (RR: 0.49, 95% CI: 0.39, 0.63) and schistosomiasis prevalence (RR: 0.50, 95% CI: 0.33, 0.75), STH intensity (SMD: -0.22, 95% CI: -0.26, -0.17), and anemia prevalence (RR: 0.87, 95% CI: 0.81, 0.94). It also improved mean hemoglobin (SMD: 0.24, 95% CI: 0.16, 0.32). We did not find any conclusive evidence from the quantitative synthesis on the relative effectiveness of integrated and non-integrated delivery strategies due to the limited data available for each subgroup. However, the qualitative synthesis from the included studies supports community-based delivery strategies and suggests that integrated prevention and control measures are more effective in achieving greater coverage compared to the routine vertical delivery, albeit it requires an existing strong healthcare infrastructure. Current evidence suggests that effective community-based strategies exist and deliver a range of preventive, promotive, and therapeutic interventions to combat helminthic neglected tropical diseases (NTDs). However, there is a need to implement and evaluate efficient integrated programs with the existing disease control programs on a larger scale throughout resource-limited regions especially to reach the unreachable.

Community based interventions for the prevention and control of Non-Helmintic NTD.

In this paper, we aim to systematically analyze the effectiveness of community based interventions (CBI) for the prevention and control of non-helminthic diseases including dengue, trypanosomiasis, chagas, leishmaniasis, buruli ulcer, leprosy and trachoma. We systematically reviewed literature published up to May 2013 and included 62 studies in this review. Findings from our review suggest that CBI including insecticide spraying; insecticide treated bednets and curtains; community education and cleanliness campaigns; chemoprophylaxis through mass drug administration; and treatment have the potential to reduce the incidence and burden of non-helminthic diseases. Lack of data limited the subgroup analysis for integrated and non-integrated delivery strategies however, qualitative synthesis suggest that integrated delivery is more effective when compared to vertical interventions; however, such integration was possible only because of the existing vertical vector control programs. Community delivered interventions have the potential to achieve wider coverage and sustained community acceptance. Eradicating these diseases will require a multipronged approach including drug administration, health education, vector control and clean water and sanitation facilities. This would require high level governmental commitment along with strong partnerships among major stakeholders.

Mitogen-activated protein kinase-activated protein kinase 2 mediates apoptosis during lung vascular permeability by regulating movement of cleaved caspase 3.

Apoptosis is a key pathologic feature in acute lung injury. Animal studies have demonstrated that pathways regulating apoptosis are necessary in the development of acute lung injury, and that activation of p38 mitogen-activated protein kinase (MAPK) is linked to the initiation of the apoptotic cascade. In this study, we assessed the role of the MAPK-activated protein kinase (MK) 2, one of p38 MAPK's immediate downstream effectors, in the development of apoptosis in an animal model of LPS-induced pulmonary vascular permeability. Our results indicate that wild-type (WT) mice exposed to LPS demonstrate increased apoptosis, as evidenced by cleavage of caspase 3 and poly (ADP-ribose) polymerase 1 and increased deoxynucleotidyl transferase-mediated dUDP nick-end labeling staining, which is accompanied by increases in markers of vascular permeability. In contrast, MK2(-/-) mice are protected from pulmonary vascular permeability and apoptosis in response to LPS. Although there was no difference in activation of caspase 3 in MK2(-/-) compared with WT mice, interestingly, cleaved caspase 3 translocated to the nucleus in WT mice while it remained in the cytosol of MK2(-/-) mice in response to LPS. In separate experiments, LPS-induced apoptosis in human lung microvascular endothelial cells was also associated with nuclear translocation of cleaved caspase 3 and apoptosis, which were both prevented by MK2 silencing. In conclusion, our data suggest that MK2 plays a critical role in the development of apoptosis and pulmonary vascular permeability, and its effects on apoptosis are in part related to its ability to regulate nuclear translocation of cleaved caspase 3.