Improvement of glymphatic-lymphatic drainage of beta-amyloid by focused ultrasound in Alzheimer's disease model.

Drainage of parenchymal waste through the lymphatic system maintains brain homeostasis. Age-related changes of glymphatic-lymphatic clearance lead to the accumulation beta-amyloid (Aß) in dementia models. In this study, focused ultrasound treatment in combination with microbubbles (FUS-MB) improved Aß drainage in early dementia model mice, 5XFAD. FUS-MB enhanced solute Aß clearance from brain, but not plaques, to cerebrospinal fluid (CSF) space and then deep cervical lymph node (dCLN). dCLN ligation exaggerated memory impairment and progress of plaque formation and also the beneficial effects of FUS-MB upon Aß removal through CSF-lymphatic routes. In this ligation model, FUS-MB improved memory despite accumulation of Aß in CSF. In conclusion, FUS-MB enhances glymphatic-lymphatic clearance of Aß mainly by increasing brain-to-CSF Aß drainage. We suggest that FUS-MB can delay dementia progress in early period and benefits of FUS-MB depend on the effect of Aß disposal through CSF-lymphatics.

Comparison of efficacy between long-pulsed Nd:YAG laser and pulsed dye laser to treat rosacea-associated nasal telangiectasia.

BACKGROUND: Rosacea is characterized by erythema on face, especially erythema and linear telangiectasia on the nose. Currently, various vascular lasers are used for treatment, and among them, are long-pulsed Nd:YAG(LPNY) and pulsed dye laser (PDL). OBJECTIVES: This study compared the efficacy of LPNY and PDL in treating rosacea-associated nasal telangiectasia. METHODS: Patients with rosacea who showed erythema and telangiectasia on the nose were included. Each patient was treated with PDL on the left side of the nasal bridge, and LPNY on the right side, three times with 4-week intervals. At the end of the treatment, two independent dermatologists evaluated overall treatment response compared with baseline. RESULTS: The physician's assessment of treatment concluded that good improvement was seen in six PDL and seven LPNY patients, and excellent improvement five PDL and four LPNY patients. There was no significant difference (p = 0.62, 95%CI) between the groups. Overall improvement was similar; however, LPNY induced a greater response in thick, dilated vessels, while erythema with mild telangiectasia was more responsive to PDL. CONCLUSION: Both LPNY and PDL are effective in treating rosacea-associated nasal telangiectasia. If LPNY is used properly to avoid side effects with careful consideration, it can also be used as a good modality.

Tracking Perfluorocarbon Nanoemulsion Delivery by 19F MRI for Precise High Intensity Focused Ultrasound Tumor Ablation.

Perfluorocarbon nanoemulsions (PFCNEs) have recently been undergoing rigorous study to investigate their ability to improve the therapeutic efficacy of tumor ablation by high intensity focused ultrasound (HIFU). For precise control of PFCNE delivery and thermal ablation, their accumulation and distribution in a tumor should be quantitatively analyzed. Here, we used fluorine-19 (19F) magnetic resonance imaging (MRI) to quantitatively track PFCNE accumulation in a tumor, and analyzed how intra-tumoral PFCNE quantities affect the therapeutic efficacy of HIFU treatment. Ablation outcomes were assessed by intra-voxel incoherent motion analysis and bioluminescent imaging up to 14 days after the procedure. Assessment of PFCNE delivery and treatment outcomes showed that 2-3 mg/mL of PFCNE in a tumor produces the largest ablation volume under the same HIFU insonation conditions. Histology showed varying degrees of necrosis depending on the amount of PFCNE delivered. 19F MRI promises to be a valuable platform for precisely guiding PFCNE-enhanced HIFU ablation of tumors.

A comparative study of pulsed dye laser versus long pulsed Nd:YAG laser treatment in recalcitrant viral warts.

BACKGROUND: Viral warts are common infectious skin disease induced by human papillomavirus (HPV). But the treatment of recalcitrant warts is still challenging. OBJECTIVE: In this study, we compared the effectiveness of pulsed dye laser (PDL) and long pulsed Nd:YAG (LPNY) laser in the treatment of recalcitrant viral warts. METHODS: We retrospectively analyzed the medical records of patients with recalcitrant warts treated with laser therapy between January 2013 and February 2016. RESULTS: Seventy-two patients with recalcitrant warts were evaluated. Thirty-nine patients were treated with pulsed dye laser and thirty-three patients were treated with LPNY laser. The following parameters were used: PDL (spot size, 7 mm; pulse duration, 1.5 ms; and fluence, 10-14 J/cm2) and LPNY (spot size, 5 mm; pulse duration, 20 ms; and fluence, 240-300 J/cm2). Complete clearance of two patients (5.1%) in PDL group, and three patients (9.1%) in LPNY group were observed without significant side effects. The patients who achieved at least 50% improvement from baseline were 20 (51.3%) in PDL and 22 (66.7%) in LPNY, respectively. CONCLUSION: This research is meaningful because we compared the effectiveness of the PDL and LPNY in the recalcitrant warts. Both PDL and LPNY laser could be used as a safe and alternative treatment for recalcitrant warts.

The effectiveness of 1,064-nm long-pulsed Nd:YAG laser in the treatment of severe onychomycosis.

INTRODUCTION: Severe onychomycosis in the elderly is a common condition and generally difficult to treat. Long-pulsed Nd:YAG (LPNY) laser has been found to be useful in the treatment of onychomycosis. We sought to evaluate the effectiveness of 1,064-nm LPNY laser in the treatment of severe onychomycosis. MATERIALS AND METHODS: Forty nails in 13 patients with severe onychomycosis were divided into two groups. Each group received eight treatment sessions at one-week intervals with 1,064-nm LPNY laser. Parameters for group A were 0.3 ms pulse duration, 5 mm spot size, 16 J/cm(2) fluence, and 10 Hz frequency, and those for group B were 0.6 ms, 2 mm, 225 J/cm(2), and 5 Hz. Clinical and mycological clearance were evaluated at 12 and 24 weeks after initial treatment. RESULTS: Clinical improvements at 12 and 24 weeks presented 47.6 and 57.1% in group A, and 26.3 and 36.8% in group B. In the treated nails with clinical improvement, mycological positive rates at 24 weeks were approximately 40% in both groups. DISCUSSION: The treatment of onychomycosis using 1,064-nm LPNY laser were incomplete in clinical and mycological improvement, and it could imply a lot of potential recurrence. We suggest that 1,064-nm LPNY laser for severe onychomycosis should need additional or combined therapy with other therapeutic options.

Extratemporal abnormalities in phosphorus magnetic resonance spectroscopy of patients with mesial temporal sclerosis.

OBJECTIVE: We evaluated extratemporal metabolic changes with phosphorus magnetic resonance spectroscopy (31P-MRS) in patients with unilateral mesial temporal sclerosis (MTS). METHOD: 31P-MRS of 33 patients with unilateral MTS was compared with 31 controls. The voxels were selected in the anterior, posterior insula-basal ganglia (AIBG, PIBG) and frontal lobes (FL). Relative values of phosphodiesters- PDE, phosphomonoesters-PME, inorganic phosphate - Pi, phosphocreatine- PCr, total adenosine triphosphate [ATPt = γ- + a- + b-ATP] and the ratios PCr/ATPt, PCr/γ-ATP, PCr/Pi and PME/PDE were obtained. RESULTS: We found energetic abnormalities in the MTS patients compared to the controls with Pi reduction bilaterally in the AIBG and ipsilaterally in the PIBG and the contralateral FL; there was also decreased PCr/γ-ATP in the ipsilateral AIBG and PIBG. Increased ATPT in the contralateral AIBG and increased γ-ATP in the ipsilateral PIBG were detected. CONCLUSION: Widespread energy dysfunction was detected in patients with unilateral MTS.

Extratemporal abnormalities in phosphorus magnetic resonance spectroscopy of patients with mesial temporal sclerosis / Anormalidades extratemporais na espectroscopia de fósforo por ressonância magnética em pacientes com esclerose mesial temporal

ABSTRACT Objective We evaluated extratemporal metabolic changes with phosphorus magnetic resonance spectroscopy (31P-MRS) in patients with unilateral mesial temporal sclerosis (MTS). Method 31P-MRS of 33 patients with unilateral MTS was compared with 31 controls. The voxels were selected in the anterior, posterior insula-basal ganglia (AIBG, PIBG) and frontal lobes (FL). Relative values of phosphodiesters- PDE, phosphomonoesters-PME, inorganic phosphate - Pi, phosphocreatine- PCr, total adenosine triphosphate [ATPt = γ- + a- + b-ATP] and the ratios PCr/ATPt, PCr/γ-ATP, PCr/Pi and PME/PDE were obtained. Results We found energetic abnormalities in the MTS patients compared to the controls with Pi reduction bilaterally in the AIBG and ipsilaterally in the PIBG and the contralateral FL; there was also decreased PCr/γ-ATP in the ipsilateral AIBG and PIBG. Increased ATPT in the contralateral AIBG and increased γ-ATP in the ipsilateral PIBG were detected. Conclusion Widespread energy dysfunction was detected in patients with unilateral MTS.

RESUMO Objetivo Nós avaliamos as alterações metabóblicas através da espectroscopia de fósforo por ressonância magnética (31P-MRS) em pacientes com esclerose mesial temporal (EMT) unilateral. Método 31P-MRS de 33 pacientes com EMT unilateral foram comparadas aos de 31 controles. Foram selecionados os voxels nas regiões insulonuclear anterior e posterior (RINA e RINP) e frontal (RF). Os valores relativos de fosfodiésteres – PDE, fosfomonoésteres- PME, fosfato inorgânico- Pi, fosfocreatina –PCr, adenosina trifosfato total [ATPt = γ- + a- + b-ATP] e as razões PCr/ATPt, PCr/γ-ATP, PCr/Pi e PME/PDE foram obtidas. Resultados Nós encontramos anormalidades em pacientes com EMT em comparação aos controles. Redução de Pi nas RINA bilateralmente, RINP ipsilateral e RF contralateral, redução de PCr/γ-ATP nas RINA e RINP ipsilaterais foram detectadas. Aumentos de ATPT na RINA contralateral e aumento de γ-ATP na RINP ipsilateral também foram encontradas. Conclusão Disfunção energética difusa foi encontrada em pacientes com EMT unilateral.

Effect of excimer laser treatment on vitiliginous areas with leukotrichia after confirmation by dermoscopy.

BACKGROUND: Leukotrichia is clinically common in patients with vitiligo, and dermoscopy is useful for finding white vellus hair. The use of phototherapy in the repigmentation of vitiliginous areas with leukotrichia is usually difficult because of a deficient melanocyte reservoir. OBJECTIVES: We sought to evaluate the effect of leukotrichia on the clinical outcomes of excimer laser treatment. METHODS: We treated 77 patients with vitiligo using excimer laser therapy. Vitiligo is classified into two types: segmental vitiligo (SV) and nonsegmental vitiligo (NSV). Before starting the treatment, we confirmed the leukotrichia of vitiliginous lesions by dermoscopy and then treated the areas once weekly for 24 weeks. At the beginning and 24 weeks later, we took clinical pictures and graded the repigmentation from 1 to 4. Grades 1 and 2 were defined as a poor response and grades 3 and 4 as a good response. RESULTS: Thirty-one of 77 patients with vitiligo had SV. Among those with SV, 24 (77.4%) had leukotrichia, and these patients showed a poor response compared to those without leukotrichia (P = 0.272). Three of 24 patients with SV and leukotrichia showed a good response. Among the 46 patients with NSV, 18 (39.1%) had leukotrichia and showed a poor response. Twenty-eight (60.9%) of the 46 patients with NSV without leukotrichia showed a good response in contrast to those with leukotrichia (P < 0.01). Comparison of the response to the excimer laser treatment, regardless of vitiligo type, showed that leukotrichia was a significant negative factor in the repigmentation of vitiliginous areas (P < 0.01). CONCLUSION: Excimer laser therapy was satisfactory in patients with vitiligo, including SV. Confirming the presence of leukotrichia in patients with vitiligo before excimer laser treatment would be helpful in predicting the response to treatment.

Photodynamic therapy using chlorophyll-a in the treatment of acne vulgaris: a randomized, single-blind, split-face study.

BACKGROUND: Chlorophyll-a is a novel photosensitizer recently tested for the treatment of acne vulgaris. OBJECTIVE: We sought to evaluate the clinical efficacy and safety of chlorophyll-a photodynamic therapy used for acne treatment. METHODS: Subjects with acne on both sides of the face were included. Eight treatment sessions were performed over a 4-week duration. Half of the face was irradiated using a blue and red light-emitting diode after topical application of chlorophyll-lipoid complex. The other half underwent only light-emitting diode phototherapy. The lesion counts and acne severity were assessed by a blinded examiner. Sebum secretion, safety, and histologic changes were also evaluated. RESULTS: In total, 24 subjects completed the study. Facial acne improved on both treated sides. On the chlorophyll-a photodynamic therapy-treated side, there were significant reductions in acne lesion counts, acne severity grades, and sebum levels compared with the side treated with light-emitting diode phototherapy alone. The side effects were tolerable in all the cases. LIMITATIONS: All the subjects were of Asian descent with darker skin types, which may limit the generalizability of the study. A chlorophyll-a arm alone is absent, as is a no-treatment arm. CONCLUSIONS: We suggest that chlorophyll-a photodynamic therapy for the treatment of acne vulgaris can be effective and safe with minimal side effects.

Widespread pH abnormalities in patients with malformations of cortical development and epilepsy: a phosphorus-31 brain MR spectroscopy study.

INTRODUCTION: Neuroimaging studies demonstrate that not only the lesions of malformations of cortical development (MCD) but also the normal-appearing parenchyma (NAP) present metabolic impairments, as revealed with (1)H-MRS. We have previously detected biochemical disturbances in MCD lesions with phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Our hypothesis is that pH abnormalities extend beyond the visible lesions. METHODS: Three-dimensional 31P-MRS at 3.0 T was performed in 37 patients with epilepsy and MCD, and in 31 matched-control subjects. The patients were assigned into three main MCD subgroups: cortical dysplasia (n=10); heterotopia (n=14); schizencephaly/polymicrogyria (n=13). Voxels (12.5 cm3) were selected in five homologous regions containing NAP: right putamen; left putamen; frontoparietal parasagittal cortex; right centrum semiovale; and left centrum semiovale. Robust methods of quantification were applied, and the intracellular pH was calculated with the chemical shifts of inorganic phosphate (Pi) relative to phosphocreatine (PCr). RESULTS: In comparison to controls and considering a Bonferroni adjusted p-value <0.01, MCD patients presented significant reduction in intracellular pH in the frontoparietal parasagittal cortex (6.985±0.022), right centrum semiovale (7.004±0.029), and left centrum semiovale (6.995±0.030), compared to controls (mean values±standard deviations of 7.087±0.048, 7.096±0.042, 7.088±0.045, respectively). Dunnet and Dunn tests demonstrated that the differences in pH values remained statistically significant in all MCD subgroups. No significant differences were found for the putamina. CONCLUSION: The present study demonstrates widespread acidosis in the NAP, and reinforces the idea that MCD visible lesions are only the tip of the iceberg.

Chemical and sensory quality of fresh pomegranate fruits exposed to gamma radiation as quarantine treatment.

The U.S. Department of Agriculture in February 2012 approved the import of fresh pomegranates subjected to irradiation as a quarantine procedure with a minimum absorbed dose of 0.4kGy against different pests. This study evaluated the application of different gamma-irradiation doses (0.4, 1, and 2kGy) in fresh pomegranate fruits and their effect on the chemical and sensory characteristics. The total soluble solids, titratable acidity, and pH values remained unaffected up to 1kGy treatment. Irradiation caused a significant decrease in the total anthocyanins and phenolic content. A strong positive correlation was observed among the antioxidant activities, total phenolics and anthocyanin contents. In general, a stronger preference was shown by sensory panelists for the juice from irradiated fruits. This study provides research-based information about the application of irradiation as a quarantine disinfestation treatment to enhance the marketing and consumer acceptance of pomegranates.

Concomitant use of an infrared fractional laser with low-dose isotretinoin for the treatment of acne and acne scars.

BACKGROUND: Acne scarring has lifelong sequelae. Fractional photothermolysis (FP) has been shown to provide fast recovery from acne within a short period, thereby aiding skin rejuvenation. Isotretinoin is a well-known, effective drug for the treatment of severe recalcitrant acne. This study investigated the safety and the efficacy of infrared fractional laser treatment in conjunction with low-dose isotretinoin for the treatment of acne and acne scars. MATERIALS: A 1550 nm Erbium-doped fiber laser was used to treat 35 patients with acne scarring. All the patients had taken isotretinoin (10 mg/day) for more than one month prior to the commencement of the fractional laser treatment. RESULTS: There was no aggravation of acne scars, hypertrophic scars, or keloids. Most of the patients (33 patients) received reduced microthermal damage zone (MTZ) treatment. Eighty percent of the treated patients (28 patients) demonstrated more than a fair improvement. The total average score on the global acne scarring classification before treatment was 13.5, and the score after treatment was 11.2. CONCLUSION: Acne and acne scars can be treated more effectively by concomitant use of an infrared fractional laser with low-dose isotretinoin with reduced MTZ densities. Most patients showed more than a fair improvement, and there was no aggravation of the scars.

Effect of intense pulsed light on rat skin.

BACKGROUND: Intense pulsed light (IPL) is widely used in treating skin conditions and has been reported to increase collagen and elastic fibers without damaging the epidermis. OBJECTIVE: To evaluate the effect of variation in the number of passes and intervals of IPL treatments on photorejuvenation in rats. MATERIALS AND METHODS: Groups of two rats each were exposed to two or four passes of an IPL source using a fluence of 30 J/cm(2) and a cut-off filter of 560 nm at 1- or 3-week intervals. The collagen and elastic fiber content in stained tissue biopsies and the thickness of the collagen fibers of IPL-irradiated and unexposed skin regions were compared. RESULTS: Collagen distribution and collagen fiber diameter was in IPL-irradiated than in control regions. The number of passes did not significantly affect the collagen fiber thickness, but the collagen fibers from the 3-week-interval groups were thicker than those of the 1-week-interval groups (p < .001). CONCLUSION: IPL increased dermal collagen fibers and collagen fiber diameter, suggesting efficacy in photorejuvenation and wrinkle reduction.