Circulating senescent myeloid cells infiltrate the brain and cause neurodegeneration in histiocytic disorders.

Neurodegenerative diseases (ND) are characterized by progressive loss of neuronal function. Mechanisms of ND pathogenesis are incompletely understood, hampering the development of effective therapies. Langerhans cell histiocytosis (LCH) is an inflammatory neoplastic disorder caused by hematopoietic progenitors expressing mitogen-activated protein kinase (MAPK)-activating mutations that differentiate into senescent myeloid cells that drive lesion formation. Some individuals with LCH subsequently develop progressive and incurable neurodegeneration (LCH-ND). Here, we showed that LCH-ND was caused by myeloid cells that were clonal with peripheral LCH cells. Circulating BRAFV600E+ myeloid cells caused the breakdown of the blood-brain barrier (BBB), enhancing migration into the brain parenchyma where they differentiated into senescent, inflammatory CD11a+ macrophages that accumulated in the brainstem and cerebellum. Blocking MAPK activity and senescence programs reduced peripheral inflammation, brain parenchymal infiltration, neuroinflammation, neuronal damage and improved neurological outcome in preclinical LCH-ND. MAPK activation and senescence programs in circulating myeloid cells represent targetable mechanisms of LCH-ND.

Mitochondrial MDM2 Regulates Respiratory Complex I Activity Independently of p53.

Accumulating evidence indicates that the MDM2 oncoprotein promotes tumorigenesis beyond its canonical negative effects on the p53 tumor suppressor, but these p53-independent functions remain poorly understood. Here, we show that a fraction of endogenous MDM2 is actively imported in mitochondria to control respiration and mitochondrial dynamics independently of p53. Mitochondrial MDM2 represses the transcription of NADH-dehydrogenase 6 (MT-ND6) in vitro and in vivo, impinging on respiratory complex I activity and enhancing mitochondrial ROS production. Recruitment of MDM2 to mitochondria increases during oxidative stress and hypoxia. Accordingly, mice lacking MDM2 in skeletal muscles exhibit higher MT-ND6 levels, enhanced complex I activity, and increased muscular endurance in mild hypoxic conditions. Furthermore, increased mitochondrial MDM2 levels enhance the migratory and invasive properties of cancer cells. Collectively, these data uncover a previously unsuspected function of the MDM2 oncoprotein in mitochondria that play critical roles in skeletal muscle physiology and may contribute to tumor progression.

Half-life and initial Solar System abundance of 146Sm determined from the oldest andesitic meteorite.

The formation and differentiation of planetary bodies are dated using radioactive decay systems, including the short-lived 146Sm-142Nd (T½ = 103 or 68 Ma) and long-lived 147Sm-143Nd (T½ = 106 Ga) radiogenic pairs that provide relative and absolute ages, respectively. However, the initial abundance and half-life of the extinct radioactive isotope 146Sm are still debated, weakening the interpretation of 146Sm-142Nd systematics obtained for early planetary processes. Here, we apply the short-lived 26Al-26Mg, 146Sm-142Nd, and long-lived 147Sm-143Sm chronometers to the oldest known andesitic meteorite, Erg Chech 002 (EC 002), to constrain the Solar System initial abundance of 146Sm. The 26Al-26Mg mineral isochron of EC 002 provides a tightly constrained initial δ26Mg* of −0.009 ± 0.005 ‰ and (26Al/27Al)0 of (8.89 ± 0.09) × 10−6. This initial abundance of 26Al is the highest measured so far in an achondrite and corresponds to a crystallization age of 1.80 ± 0.01 Myr after Solar System formation. The 146Sm-142Nd mineral isochron returns an initial 146Sm/144Sm ratio of 0.00830 ± 0.00032. By combining the Al-Mg crystallization age and initial 146Sm/144Sm ratio of EC 002 with values for refractory inclusions, achondrites, and lunar samples, the best-fit half-life for 146Sm is 102 ± 9 Ma, corresponding to the physically measured value of 103 ± 5 Myr, rather than the latest and lower revised value of 68 ± 7 Ma. Using a half-life of 103 Ma for 146Sm, the 146Sm/144Sm abundance of EC 002 translates into an initial Solar System 146Sm/144Sm ratio of 0.00840 ± 0.00032, which represents the most reliable and precise estimate to date and makes EC 002 an ideal anchor for the 146Sm-142Nd clock.

Real-time measurements of ATP dynamics via ATeams in Plasmodium falciparum reveal drug-class-specific response patterns.

Malaria tropica, caused by the parasite Plasmodium falciparum (P. falciparum), remains one of the greatest public health burdens for humankind. Due to its pivotal role in parasite survival, the energy metabolism of P. falciparum is an interesting target for drug design. To this end, analysis of the central metabolite adenosine triphosphate (ATP) is of great interest. So far, only cell-disruptive or intensiometric ATP assays have been available in this system, with various drawbacks for mechanistic interpretation and partly inconsistent results. To address this, we have established fluorescent probes, based on Förster resonance energy transfer (FRET) and known as ATeam, for use in blood-stage parasites. ATeams are capable of measuring MgATP2- levels in a ratiometric manner, thereby facilitating in cellulo measurements of ATP dynamics in real-time using fluorescence microscopy and plate reader detection and overcoming many of the obstacles of established ATP analysis methods. Additionally, we established a superfolder variant of the ratiometric pH sensor pHluorin (sfpHluorin) in P. falciparum to monitor pH homeostasis and control for pH fluctuations, which may affect ATeam measurements. We characterized recombinant ATeam and sfpHluorin protein in vitro and stably integrated the sensors into the genome of the P. falciparum NF54attB cell line. Using these new tools, we found distinct sensor response patterns caused by several different drug classes. Arylamino alcohols increased and redox cyclers decreased ATP; doxycycline caused first-cycle cytosol alkalization; and 4-aminoquinolines caused aberrant proteolysis. Our results open up a completely new perspective on drugs' mode of action, with possible implications for target identification and drug development.

Monovalent cation binding to model systems and the macrocyclic depsipeptide, emodepside.

This study focuses on the systematic exploration of the emodepside conformations bound to monovalent K+ ion using quantum mechanical density functional theory (DFT) calculations at the M06-2X/6-31+G(d,p) level of theory. Nine conformers of emodepside and their complexes with K+ ion were characterized as stationary points on the potential energy surface. The conformational isomers were examined for their 3D structures, bonding, energetics, and interactions with the cation. A cavitand-like structure (CC) is identified to be the energetically most stable arrangement. To arrive at a better understanding of the K+ ion binding, calculations were initially performed on complexes formed by the K+ and Na+ ions with model ligands (methyl ester and N,N-dimethyl acetamide). Both the natural bond orbital (NBO) method and the block-localized wavefunction (BLW) energy decomposition approach was employed to assess the bonding and energetic contributions stabilizing the ion-bound model complexes. Finally, the solvent effect was evaluated through complete geometry optimizations and energy minimizations for the model ion-ligand complexes and the emodepside-K+ bound complexes using an implicit solvent model mimicking water and DMSO.

A Novel Perspective on Enhancing Photocatalytic Performance through the Synergistic Effect of Nd Single Atoms and Heterostructures.

There are few reports on lanthanide single atom modified catalysts, as the role of the 4f levels in photocatalysis is difficult to explain clearly. Here, the synergistic effect of 4f levels of Nd and heterostructures is studied by combining steady-state, transient, and ultrafast spectral analysis techniques with DFT theoretical calculations based on the construction of Nd single atom modified black phosphorus/g-C3N4 (BP/CN) heterojunctions. As expected, the generation rates of CO and CH4 of the optimized heterostructure are 7.44 and 6.85 times higher than those of CN, and 8.43 and 9.65 times higher than those of BP, respectively. The Nd single atoms can not only cause surface reconstruction and regulate the active sites of BP, but also accelerate charge separation and transfer, further suppressing the recombination of electron-hole pairs. The electrons can transfer from g-C3N4:Nd to BP:Nd, with a transfer time of ≈11.4 ps, while the radiation recombination time of electron-hole pairs of g-C3N4 is ≈26.13 µs, indicating that the construction of heterojunctions promotes charge transfer. The 2P1/2/2G9/2/4G7/2/2H11/2/4F7/2→4I9/2 emissions from Nd3+ can also be absorbed by heterostructures, which improves the utilization of light. The energy change of the key rate measurement step CO2 *→COOH* decreases through Nd single atom modification.

3D imaging of magnetic domains in Nd2Fe14B using scanning hard X-ray nanotomography.

Nanoscale structural and electronic heterogeneities are prevalent in condensed matter physics. Investigating these heterogeneities in 3D has become an important task for understanding material properties. To provide a tool to unravel the connection between nanoscale heterogeneity and macroscopic emergent properties in magnetic materials, scanning transmission X-ray microscopy (STXM) is combined with X-ray magnetic circular dichroism. A vector tomography algorithm has been developed to reconstruct the full 3D magnetic vector field without any prior noise assumptions or knowledge about the sample. Two tomographic scans around the vertical axis are acquired on single-crystalline Nd2Fe14B pillars tilted at two different angles, with 2D STXM projections recorded using a focused 120 nm X-ray beam with left and right circular polarization. Image alignment and iterative registration have been implemented based on the 2D STXM projections for the two tilts. Dichroic projections obtained from difference images are used for the tomographic reconstruction to obtain the 3D magnetization distribution at the nanoscale.

Q-switched 1064 nm Nd: YAG laser restores skin photoageing by activating autophagy by TGFß1 and ITGB1.

Excessive ultraviolet B ray (UVB) exposure to sunlight results in skin photoageing. Our previous research showed that a Q-switched 1064 nm Nd: YAG laser can alleviate skin barrier damage through miR-24-3p. However, the role of autophagy in the laser treatment of skin photoageing is still unclear. This study aims to investigate whether autophagy is involved in the mechanism of Q-switched 1064 nm Nd: YAG in the treatment of skin ageing. In vitro, primary human dermal fibroblast (HDF) cells were irradiated with different doses of UVB to establish a cell model of skin photoageing. In vivo, SKH-1 hairless mice were irradiated with UVB to establish a skin photoageing mouse model and irradiated with laser. The oxidative stress and autophagy levels were detected by western blot, immunofluorescence and flow cytometer. String was used to predict the interaction protein of TGF-ß1, and CO-IP and GST-pull down were used to detect the binding relationship between TGFß1 and ITGB1. In vitro, UVB irradiation reduced HDF cell viability, arrested cell cycle, induced cell senescence and oxidative stress compared with the control group. Laser treatment reversed cell viability, senescence and oxidative stress induced by UVB irradiation and activated autophagy. Autophagy agonists or inhibitors can enhance or attenuate the changes induced by laser treatment, respectively. In vivo, UVB irradiation caused hyperkeratosis, dermis destruction, collagen fibres reduction, increased cellular senescence and activation of oxidative stress in hairless mice. Laser treatment thinned the stratum corneum of skin tissue, increased collagen synthesis and autophagy in the dermis, and decreased the level of oxidative stress. Autophagy agonist rapamycin and autophagy inhibitor 3-methyladenine (3-MA) can enhance or attenuate the effects of laser treatment on the skin, respectively. Also, we identified a direct interaction between TGFB1 and ITGB1 and participated in laser irradiation-activated autophagy, thereby inhibiting UVB-mediated oxidative stress further reducing skin ageing. Q-switched 1064 nm Nd: YAG laser treatment inhibited UVB-induced oxidative stress and restored skin photoageing by activating autophagy, and TGFß1 and ITGB1 directly incorporated and participated in this process.

The Pulsed Nd:YAG Laser Therapy Enhanced Nerve Regeneration via Apoptosis Inhibition in a Rat Crushed Sciatic Nerve Model.

The study was aimed to validate the efficacy of the pulsed Nd:YAG laser on nerve regeneration in a rat sciatic nerve crushed model. 54 Wistar rats were randomly assigned into three groups: shame control, crush control, and laser treated group. For the laser treated group, the pulsed Nd:YAG laser (10 Hz) with 350 mJ per pulse in energy density and 50 J/cm2 in fluence was applied extracorporeally at the lesion site for 12 min to daily deliver 500 J immediately and consecutive 9 days following the crush injury. At week 1, the apoptosis-related activities in the injured nerve were examined (n = 8/each group). The sciatic functional index (SFI) was measured preoperatively and weekly until 4 weeks after the index procedure. The injured nerve and the innervated gastrocnemius muscle histology were assessed at week 4 (n = 10/each group). At week 1, the laser group showed the significant less TUNEL-positive ratio (P < 0.05), and the lower expression of cleaved caspase3/procaspase-3 and beclin-2/beclin-2-associated protein X ratios compared with the crush control. Furthermore, the laser group revealed significantly better SFI since week 1 and throughout the study (P < 0.05, all) compared with the crush control. At week 4, the laser group showed significantly higher axon density, lower myelin g-ratio, and the corresponding higher glycogen expression (P < 0.05, all) in the gastrocnemius muscle compared with those in the crush control. The pulsed Nd:YAG might enhance the injured nerve regeneration via apoptosis inhibition.

Adjuvant re-irradiation vs. no early re-irradiation of resected recurrent glioblastoma: pooled comparative cohort analysis from two tertiary centers.

BACKGROUND: The optimal management strategy for recurrent glioblastoma (rGBM) remains uncertain, and the impact of re-irradiation (Re-RT) on overall survival (OS) is still a matter of debate. This study included patients who achieved gross total resection (GTR) after a second surgery after recurrence, following the GlioCave criteria. METHODS: Inclusion criteria include being 18 years or older, having histologically confirmed locally recurrent IDHwt or IDH unknown GBM, achieving MRI-proven GTR after the second surgery, having a Karnofsky performance status of at least 60% after the second surgery, having a minimum interval of 6 months between the first radiotherapy and the second surgery, and a maximum of 8 weeks from second surgery to the start of Re-RT. RESULTS: A total of 44 patients have met the inclusion criteria. The median OS after the second surgery was 14 months. All patients underwent standard treatment after initial diagnosis, including maximum safe resection, adjuvant radiochemotherapy and adjuvant chemotherapy. Re-RT did not significantly impact OS. However, MGMT promoter methylation status and a longer interval (> 12 months) between treatments were associated with better OS. Multivariate analysis revealed the MGMT status as the only significant predictor of OS. CONCLUSION: Factors such as MGMT promoter methylation status and treatment interval play crucial roles in determining patient outcomes after second surgery. Personalized treatment strategies should consider these factors to optimize the management of rGBM. Prospective research is needed to define the value of re-RT after second surgery and to inform decision making in this situation.

Threefold enhanced photodegradation of methylene blue using MgO composite with minimum Nd2O3: finding the sweet spot.

Removal of organic dyes like methylene blue (MB) from industrial effluents serves as potential source of potable water. Photocatalytic degradation using sustainable catalyst is deemed to be an affordable solution. In this work, Nd2O3/MgO nanocomposite with different compositions (1, 3, and 5wt% Nd2O3 with MgO) have been achieved using hydrothermal synthesis and characterized extensively. Interestingly, increasing Nd2O3 proportion (1-5%) enhances light absorption, and decreases band gap and electron-hole recombination. The efficacy of the photocatalysts is tested with the degradation of MB dye, through optimizing Nd2O3/MgO proportion, contact time, catalyst dose, and pH. Interestingly, control experiments reveal that 5wt% Nd2O3/MgO achieve 99.6% degradation of MB in 90 min at pH 7, compared to 88.8% with bare MgO under same condition. Kinetic data show that 5wt% Nd2O3/MgO exhibits ca. 3 times higher degradation rate compared to MgO. For the first time, our work enable MgO-based sustainable photocatalyst development with minimum (5 wt%) rare-earth combination to achieve excellent photocatalytic degradation performance.

Nd:YAG/Er:YAG dual laser compared with topical steroid to treat vulvar lichen sclerosus: A randomised controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of a novel non-ablative Nd:YAG/Er:YAG dual laser treatment for vulvar lichen sclerosus (LS) in comparison with the recommended first-line therapy with topical steroid. DESIGN: A randomised investigator-initiated active-controlled trial. SETTING: Single tertiary referral centre. POPULATION: Women with vulvar LS. METHODS: Randomisation (2:1) to Nd:YAG/Er:YAG laser therapy or topical clobetasol proprionate therapy. Four laser treatments at 0, 1, 2 and 4 months or decreasing doses of steroid for 6 months. MAIN OUTCOME MEASURES: The primary outcome was the change in objective validated clinical LS score in the laser arm between baseline and 6 months. Secondary outcomes were laser tolerability/safety, symptom scores and patient satisfaction. RESULTS: Sixty-six women were included, 44 in the laser group and 22 in the steroid group. The total LS score decreased by -2.34 ± 1.20 (95% CI -2.71 to -1.98) in women treated with laser compared with a decrease of -0.95 ± 0.90 (95% CI -1.35 to -0.56) in those receiving steroid applications (p < 0.001). Laser treatment was safe and well tolerated. Subjective severity scores (on visual analogue scale) and vulvovaginal symptoms questionnaire scores improved similarly for the laser and steroid arms without significant differences between the two treatments. Patient satisfaction was higher in the laser arm than in the steroid arm (p = 0.035). CONCLUSIONS: Non-ablative dual Nd:YAG/Er:YAG laser therapy was safe and significantly improved clinical outcome and subjective symptoms at the 6-month follow up. This suggests that laser may be a promising alternative to corticosteroid therapy. However, the authors caution regular follow ups because of the premalignant nature of the disease.

Evolutionary characteristics of the mitochondrial NADH dehydrogenase subunit 6 gene in some populations of four sympatric Mustela species (Mustelidae, Mammalia) from central Europe.

BACKGROUND: Selection on or reticulate evolution of mtDNA is documented in various mammalian taxa and could lead to misleading phylogenetic conclusions if not recognized. We sequenced the MT-ND6 gene of four sympatric Mustelid species of the genus Mustela from some central European populations. We hypothesised positive selection on MT-ND6, given its functional importance and the different body sizes and life histories of the species, even though climatic differences may be unimportant for adaptation in sympatry. METHODS AND RESULTS: MT-ND6 genes were sequenced in 187 sympatric specimens of weasels, Mustela nivalis, stoats, M. erminea, polecats, M. putorius, and steppe polecats, M. eversmannii, from eastern Austria and of fourteen allopatric polecats from eastern-central Germany. Median joining networks, neighbour joining and maximum likelihood analyses as well as Bayesian inference grouped all species according to earlier published phylogenetic models. However, polecats and steppe polecats, two very closely related species, shared the same two haplotypes. We found only negative selection within the Mustela sequences, including 131 downloaded ones covering thirteen species. Positive selection was observed on three MT-ND6 codons of other mustelid genera retrieved from GenBank. CONCLUSIONS: Negative selection for MT-ND6 within the genus Mustela suggests absence of both environmental and species-specific effects of cellular energy metabolism despite large species-specific differences in body size. The presently found shared polymorphism in European polecats and steppe polecats may result from ancestral polymorphism before speciation and historical or recent introgressive hybridization; it may indicate mtDNA capture of steppe polecats by M. putorius in Europe.

Analysis of Genetic Structure and Genetic Diversity in Japanese Grey-Headed Lapwing Population Using mtDNA.

The grey-headed lapwing (Vanellus cinereus) is a wading species in East Asia. However, examples of regional population dynamics and genetic research are limited. To reconsider the natural history and current status of the grey-headed lapwing in Japan, we analyzed the genetic diversity of the Japanese grey-headed lapwing population. We collected 77 grey-headed lapwing samples from 12 locations across Japan during the breeding season and three individuals during the wintering season and extracted DNA; 496-bp sequences of the ND2, which form part of the mitochondrial DNA, were determined for genetic analysis of the population. Consequently, 10 haplotypes were detected in 80 individuals, and 67 individuals, 84% of the total, shared two haplotypes, namely Vc1 and Vc2. Furthermore, the results showed that the prevalence of Vc1 was higher mainly in northern Japan, while that of Vc2 was higher mainly in southern Japan. Genetic diversity analysis showed that the overall haplotype diversity in Japan was 0.617, which is not particularly low. The sequence of Vc1 was exactly the same as that of grey-headed lapwing in China. Our study revealed the genetic structure of the grey-headed lapwing, suggesting that as the grey-headed lapwing expanded its distribution area into southern Japan, many Vc2-positive individuals migrated southward, resulting in a higher detection rate of Vc2 in southern Japan.

No side effects on rabbit retina or vitreous microenvironment by nd:YAG laser vitreolysis.

BACKGROUND: To explore the safety of Neodymium:Yttrium-aluminum-garnet (Nd:YAG) laser vitreolysis based on the histological examination of the retina and the alteration of vitreous cytokines in the rabbits. METHODS: Nine male New Zealand rabbits underwent Nd:YAG laser vitreolysis of 10 mJ x 500 pulses in the left eyes, while the right eyes were used as controls. Intraocular pressure, color fundus photography, and ultrasound B scan were measured before, as well as 1 day, 4 weeks, and 12 weeks after Nd:YAG laser vitreolysis. Three rabbits were euthanized 1 day, 4 weeks, and 12 weeks after treatment, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and hematoxylin-eosin (H&E) staining were used to look for pathological changes in the retina. An enzyme-linked immunosorbent assay (ELISA) was utilized to detect the expression of vascular endothelial growth factor (VEGF) and some inflammatory cytokines, including interferon inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1) and interlenkin 6 (IL-6) in the vitreous humor. The ascorbic acid (AsA) and total reactive antioxidant potential (TRAP) in the vitreous humor were also measured. RESULTS: Following Nd:YAG laser vitreolysis, the levels of VEGF, IP-10, MCP-1, IL6, AsA, and TRAP in the vitreous humor did not change substantially (P > 0.05). There were no detectable pathological changes in the retinal tissues, and no apoptotic signal was found. CONCLUSIONS: Rabbits tolerate Nd:YAG laser vitreolysis without observable impact on retinal tissue or the microenvironment of the vitreous.

The investigation and comparison of the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated infraorbital dark circles and wrinkles: A controlled blinded randomized clinical trial.

BACKGROUND: To evaluate the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated dark circles and wrinkles under the eyes. METHOD: This study was a single-blinded randomized clinical trial conducted on patients with suborbital darkening under the eyes that randomly divided into control and case groups. In the control group, 15 patients were treated with one session of nanofat injection only, and five patients of each intervention groups received one session of nanofat+SVF injection, nanofat+PRP injection, and nanofat injection+Nd:YAG laser, respectively. Assessments methods were (1) evaluation of the degree of darkness and repair under the eyes by a blinded dermatologist based on clinical photographs, (2) investigating patient satisfaction, (3) using biometric variables for color, thickness, and density of the skin (only 3 months after the treatment), and (4) recording the possible adverse effects. CONCLUSION: In terms of the extent of reduction in the intensity of darkness under the eyes, the combined treatment of nanofat injection together with SVF, PRP, and Nd:YAG laser had a much greater therapeutic effect than nanofat injection alone. In all three groups of combined treatments, patients were 100% satisfied. In terms of biometric variables, amount of changes in colorimeter, complete and dermal thickness, complete and dermal density, between the different groups was statistically significant. The use of combined treatments including nanofat with SVF injection, PRP, and 1064 Q-switched Nd:YAG laser may be more effective than nanofat alone, in reducing infraorbital dark circles and wrinkles.

Optical Effects of Focused Fractional Nanosecond 1064-nm Nd:YAG Laser: Techniques of Application on Human Skin.

BACKGROUND AND OBJECTIVES: Considering the pulse widths of picosecond and nanosecond lasers used in cutaneous laser surgery differ by approximately one order of magnitude, can nanosecond lasers produce the optical effect in human skin similar to laser-induced optical breakdown (LIOB) caused by picosecond lasers? METHODS: Cutaneous changes induced by a focused fractional nanosecond 1064-nm Nd:YAG laser were evaluated by VISIA-CR imaging, histological examination, and harmonic generation microscopy (HGM). RESULTS: A focused fractional nanosecond 1064-nm Nd:YAG laser can generate epidermal vacuoles or dermal cavities similar to the phenomenon of LIOB produced by picosecond lasers. The location and extent of photodisruption can be controlled by the laser fluence and focus depth. Moreover, laser-induced shock wave propagation and thermal degeneration of papillary collagen can be observed by HGM imaging. CONCLUSION: Focused fractional nanosecond lasers can produce an optical effect on human skin similar to LIOB caused by picosecond lasers. With techniques of application, the treatment can induce epidermal and dermal repair mechanisms in a tunable fashion to improve skin texture, wrinkles, scars, and dyspigmentation, without disrupting the epidermal surface.

Comparison of 755-nm picosecond alexandrite laser versus 1064-nm Q-switched Nd:YAG laser for melasma: A randomized, split-face controlled, 2-year follow-up study.

OBJECTIVES: Pulsed laser treatment of melasma has shown some promising results. To compare the effectiveness and safety of 755-nm picosecond alexandrite laser (PSAL) fitted with diffractive lens array (DLA) versus 1064-nm Q-switched neodynimum:yttrium aluminum garnet laser (QSNYL) for the treatment of melasma. METHODS: We conducted a randomized, split face controlled, 2-year follow-up study. Each face was divided into two parts, each side receiving three treatments with either PSAL or QSNYL at 1 month intervals. Modified Melasma Area Severity Index scores (mMASI), pain scores, patient satisfaction and adverse events were recorded. In vivo reflectance confocal microscopy (RCM) images were acquired. RESULTS: Twenty subjects were enrolled and three dropped out. At 6 months, mMASI scores were significantly lower than baseline for QSNYL sides (p = 0.022), with no statistically significant difference between PSAL sides before and after treatment, PSAL sides versus QSNYL sides, or patient satisfaction scores. QSNYL treatment was associated with less pain (p = 0.014). No serious adverse events were reported. In the PSAL sides RCM showed a large number of dendritic melanocytes infiltrated in the dermis at 2 weeks and 4 weeks after treatment. Ten patients (58.82%) reported recurrence or exacerbation at 2-year follow-up with no statistically significant difference between the two lasers. CONCLUSIONS: QSNYL demonstrated short term clinical efficacy for melasma, but did not provide any additional benefit compared to PSAL with DLA. QSNYL was associated with less pain. There was a high recurrence rate at 2-year follow-up. RCM allowed the detection of cellular changes in melasma lesions.

Nd:YAG 1064 nm laser treatment for onychomycosis - is it really effective? A prospective assessment for efficiency and factors contributing to response.

Onychomycosis is a highly prevalent and persistent nail disorder primarily caused by dermatophytes. The effectiveness of current topical and systemic antifungals is limited by the extent and severity of the infection, patient demographics and health status, hepatic toxicity, drug interactions and low compliance. Laser therapy is a promising modality for safe and cost-effective removal of mycotic nail. This prospective study assessed the performance of a multi-series long-pulsed Nd:YAG 1064 nm regimen (30-40 J/cm2 , 1 Hz) in the treatment of 213 mycotic nails in 31 patients. Pain and discomfort were scored at each treatment session and mycological and clinical cure rates were determined 3 months after the last treatment session. Patients presented with mostly severe (mean SCIO score: 21.9 ± 8.9), T. rubrum-positive (87.1%) infections. Most (61%) had a family history of onychomycosis and a significant proportion had comorbidities, including hypertension (38.7%), hyperlipidemia (35.5%) and/or diabetes (12.9%). Treatment was well tolerated and there were no reports of nail deformity or burns. By 3 months post-treatment, mycological cure was achieved by 4 (12.9%) and visual improvements were noted for 10 (32.3%) patients, including 3 (9.7%) with moderate to significant improvements. Clinical response correlated with baseline SCIO ≤ 20 (OR: 0.9 [0.13-6.52]), family history of onychomycosis (OR: 0.27 [0.04-1.50]) and comorbidities (OR: 0.44 [0.05-3.74]). In conclusion, Nd:YAG 1064 nm laser is safe and effective for the management of mild-to-moderate onychomycosis in diverse populations. Further studies will be necessary to adjust treatment parameters to patient and nail profiles and to determine the impact of combined laser and topical therapies.

Soranus of Ephesus (98-138 ad) and his contributions on human embryology, paediatrics and obstetric knowledge.

This study describes the life and works of Soranus of Ephesus (98-138 AD) who was born in Ephesus in Asia Minor and he practiced medicine in Alexandria and Rome in the Roman period (1st/2nd century AD). Although the majority of his writings have been lost, his surviving popular scientific textbook, a four-volume treatise on "Gynecology", describes ancient medical practice regarding human embryology, paediatrics and obstetrics.