Repetitive Transcranial Magnetic Stimulation in Fibromyalgia: Exploring the Necessity of Neuronavigation for Targeting New Brain Regions.

Fibromyalgia and osteoarthritis are among the most prevalent rheumatic conditions worldwide. Nonpharmacological interventions have gained scientific endorsements as the preferred initial treatments before resorting to pharmacological modalities. Repetitive transcranial magnetic stimulation (rTMS) is among the most widely researched neuromodulation techniques, though it has not yet been officially recommended for fibromyalgia. This review aims to summarize the current evidence supporting rTMS for treating various fibromyalgia symptoms. Recent findings: High-frequency rTMS directed at the primary motor cortex (M1) has the strongest support in the literature for reducing pain intensity, with new research examining its long-term effectiveness. Nonetheless, some individuals may not respond to M1-targeted rTMS, and symptoms beyond pain can be prominent. Ongoing research aims to improve the efficacy of rTMS by exploring new brain targets, using innovative stimulation parameters, incorporating neuronavigation, and better identifying patients likely to benefit from this treatment. Summary: Noninvasive brain stimulation with rTMS over M1 is a well-tolerated treatment that can improve chronic pain and overall quality of life in fibromyalgia patients. However, the data are highly heterogeneous, with a limited level of evidence, posing a significant challenge to the inclusion of rTMS in official treatment guidelines. Research is ongoing to enhance its effectiveness, with future perspectives exploring its impact by targeting additional areas of the brain such as the medial prefrontal cortex, anterior cingulate cortex, and inferior parietal lobe, as well as selecting the right patients who could benefit from this treatment.

Comparison of Intense Pulsed Light Treatments including Upper Lid or Lateral Canthus in Patients of Meibomian Gland Dysfunction.

Background: To determine the differences in the effects of intense pulsed light (IPL) treatment when including the upper and lower lid or lateral canthus area in patients with meibomian gland dysfunction (MGD). Methods: Patients who underwent three IPL treatment sessions at 3-week intervals were divided into three groups according to the treatment sites: group A, lower lid; group B, upper and lower lids; and group C, lower lid and lateral canthal area. Before and after the IPL treatment sessions, we obtained the lid abnormality score (LAS), meibum expressibility (ME), meibum quality (MQ), lipid layer thickness (LLT), type I Schirmer test (ST), tear break-up time (TBUT) test, corneal fluorescein staining scores (CFSs), and Ocular Surface Disease Index (OSDI). Results: IPL treatment significantly improved LASs, ME, MQ, TBUT, CFS, and OSDI values in all groups. Differences in LAS values before and after IPL treatment were significantly greater in groups B and C than those in group A. Conclusions: IPL treatment encompassing the upper lid and lateral canthus together with the lower lid elicited additional improvement in patients with MGD. The additional effect on treating the lateral canthus was similar to the effect observed on the additional treatment of the upper lid.

Interprofessional learning in practice-based settings: AMEE Guide No. 169.

The provision of optimum health care services requires collaboration of health care professionals in integrated interprofessional (IP) teams. This guide addresses the practical aspects of establishing and delivering pre-licensure IP programs to prepare graduates of health professional programs to work in teams and wider collaboration, and consequently enhance the quality of health care. The main updated IP frameworks are presented to highlight commonalities that represent the essential competencies and outcomes of programs implementing interprofessional education (IPE). We discuss how these may be adapted to the local context, and present examples of models of implementation to guide the initial steps of establishing similar programs. Examples of pre-licensure IP practice-based learning, such as community-based, simulation-based, student-run and led clinics, and interprofessional training wards, and post-licensure interprofessional learning (IPL), are described. We consider assessment of IPL along the continuum of learning IP. This guide also emphasises the need to tailor faculty development programs for local contexts and consider factors affecting sustainability such as funding and accreditation. We finish with the governance of IP programs and how global IP networks may support interprofessional practice-based learning from development to delivery.

Intraoral laser hair removal: A scoping review.

PURPOSE: Intraoral hair growth is a debilitating side effect of flap or graft-based oropharyngeal reconstruction. There is no standardized treatment, but groups have successfully eradicated unwanted hair growth with intraoral laser hair removal. This scoping review assesses the utility of laser therapy in managing this condition. METHODS: This scoping review followed PRISMA-ScR guidelines. Ovid Medline, Embase (Ovid) and Scopus were queried using index terms and keywords. Resulting articles were reviewed for inclusion by two independent reviewers against inclusion criteria and relevant data were extracted. RESULTS: The literature search yielded 297 articles, 22 of which met inclusion criteria. In total, 77 patients were treated: 38 patients with an Alexandrite laser, 19 with an Nd:YAG laser, 18 with a diode laser, and two with a CO2 laser. Complete response defined as 80% or more reduction in hair count was achieved in 70 patients (90%) and six patients (8%) achieved a partial response (10%-79% reduction in hair count). One patient (1%) with gray hair saw less than a 10% reduction in hair count. On average, 3.84 treatment sessions were needed, spaced 5.4 weeks apart. Treatments were well tolerated without major side effects. CONCLUSIONS: This is the first scoping review assessing the utility of intraoral laser hair therapy and suggests it may be a safe and effective treatment. However, surgeons should advise preoperative hair removal when clinically feasible to mitigate this side effect as much as possible.

TAFRO Syndrome: A Syndrome or a Subtype of Multicentric Castleman Disease?

TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis of bone marrow/renal dysfunction, organomegaly) syndrome is a systemic inflammatory disorder of unknown etiology. It has been recognized as a subtype of idiopathic multicentric Castleman disease (iMCD), and the international diagnostic criteria for iMCD-TAFRO require a lymph node histopathology consistent with iMCD. Furthermore, TAFRO syndrome is defined as a heterogeneous clinical entity caused by underlying diseases such as malignancy, autoimmune diseases, or infections. However, the cases that led to the proposal of TAFRO syndrome lacked recognizable lymphadenopathy and were inconsistent with any other diseases, despite vigorous efforts in differential diagnosis. Irrespective of the presence or absence of Castleman disease (CD)-like histology, TAFRO syndrome exhibits homogeneous clinical, laboratory, and prognostic features, setting it apart from iMCD without TAFRO syndrome. Defining iMCD-TAFRO apart from TAFRO syndrome is deemed meaningless and confusing. MCD is a heterogeneous lymphoproliferative disorder consisting of several subtypes with different pathogenesis, clinical manifestations, and histological features. Typical MCD in Japan, characterized by the histology of plasma cell type and marked polyclonal hypergammaglobulinemia, is identical to idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL). Although IPL is classified into iMCD-NOS (not otherwise specified), it should be recognized as a distinct clinicopathological entity. Furthermore, we propose to separate TAFRO syndrome from the MCD category as a defined disorder.

Comparative In Vivo Imaging of Retinal Structures in Tree Shrews, Humans, and Mice.

Rodent models, such as mice and rats, are commonly used to examine retinal ganglion cell damage in eye diseases. However, as nocturnal animals, rodent retinal structures differ from primates, imposing significant limitations in studying retinal pathology. Tree shrews (Tupaia belangeri) are small, diurnal paraprimates that exhibit superior visual acuity and color vision compared with mice. Like humans, tree shrews have a dense retinal nerve fiber layer (RNFL) and a thick ganglion cell layer (GCL), making them a valuable model for investigating optic neuropathies. In this study, we applied high-resolution visible-light optical coherence tomography to characterize the tree shrew retinal structure in vivo and compare it with that of humans and mice. We quantitatively characterize the tree shrew's retinal layer structure in vivo, specifically examining the sublayer structures within the inner plexiform layer (IPL) for the first time. Next, we conducted a comparative analysis of retinal layer structures among tree shrews, mice, and humans. We then validated our in vivo findings in the tree shrew inner retina using ex vivo confocal microscopy. The in vivo and ex vivo analyses of the shrew retina build the foundation for future work to accurately track and quantify the retinal structural changes in the IPL, GCL, and RNFL during the development and progression of human optic diseases.

Effective Treatment of Rosacea and Other Vascular Lesions Using Intense Pulsed Light System Emitting Vascular Chromophore-Specific Wavelengths: A Clinical and Dermoscopical Analysis.

Background: Facial telangiectasias is a prevalent cosmetic disorder that can be associated with several conditions such as rosacea. IPL (intensity pulsed light) therapy is commonly used for the treatment of vascular lesions. This study tested the efficacy of an IPL system emitting selected vascular chromophore-specific wavelengths in the range of 500-1200 nm for the treatment of vascular lesions. Materials and Methods: A total of 39 patients affected by different vascular lesions on their face were enrolled. The procedure consisted of three treatment sessions, spaced 1 month apart, using the IPL system with a 500-677 and 854-1200 nm filter. Follow-up was performed at 21-90 days (3 weeks-3 months) after the last IPL session. Three-dimensional and dermoscopic clinical photographs were captured and evaluated using a five-point scale. Adverse events were checked. Results: In total, 21 patients achieved excellent improvement, 13 patients achieved good improvement, 3 patients achieved moderate improvement, 2 patients achieved mild improvement, and 0 patients achieved no improvement, with an overall good response to treatment. The photographic evaluation showed good results as soon as 3 days after the last IPL session. Relevant side effects were absent. Conclusions: The study device may represent a successful treatment to improve vascular lesions that are resistant to laser therapy.

A prospective, split-face, randomized controlled trial of intense pulsed light-photodynamic therapy for seborrhea.

BACKGROUND: Seborrhea poses a common cosmetic concern in adolescents and young adults, often accompanied by enlarged pores, and contributing to various skin conditions, including acne vulgaris and seborrheic dermatitis. At present, there is a lack of effective treatment for this problem, and the potential of photodynamic therapy (PDT) in reducing sebum remains inconclusive. OBJECTIVE: This exploratory, prospective, single-center, double-blinded, randomized split-face controlled trial aimed to compare the efficacy and safety of intense pulsed light-photodynamic therapy (IPL-PDT) versus IPL therapy for seborrhea. METHODS: Participants with seborrhea underwent 3 times of IPL treatment (590 nm, 15-17 J/cm2 based on patient's tolerance) for one hemifacial part and IPL-PDT treatment for the other. Follow-up assessment was conducted up to 8 weeks after the final treatment. RESULTS: Compared with single IPL treatment, IPL-PDT can significantly inhibit sebum secretion and decrease pore size. PDT group exhibited no additional damage to the skin barrier, with even lower transepidermal water loss (TEWL). Additionally, the PDT group showed superior improvement in scores of porphyrins, red areas, and ultraviolet (UV) spots. Both groups experienced only mild topical adverse effects, well tolerated by the participants. CONCLUSION: IPL-PDT is a more effective method than IPL in the treatment of seborrhea, as well as on the improvement of the skin barrier function.

Pre-scan state anxiety is associated with greater right amygdala-hippocampal response to fearful versus happy faces among trait-anxious Latina girls.

BACKGROUND: Unfamiliarity with academic research may contribute to higher levels of anticipatory state anxiety about affective neuroimaging tasks. Children with high trait anxiety display differences in brain response to fearful facial affect compared to non-anxious youth, but little is known about the influence of state anxiety on this association. Because reduced engagement in scientific research and greater mistrust among minoritized groups may lead to systematic differences in pre-scan state anxiety, it is crucial to understand the neural correlates of state anxiety during emotion processing so as to disambiguate sources of individual differences. METHODS: The present study probed the interactive effects of pre-scan state anxiety, trait anxiety, and emotional valence (fearful vs. happy faces) on neural activation during implicit emotion processing in a community sample of 46 preadolescent Latina girls (8-13 years). RESULTS: Among girls with mean and high levels of trait anxiety, pre-scan state anxiety was associated with greater right amygdala-hippocampal and left inferior parietal lobe response to fearful faces relative to happy faces. CONCLUSIONS: Anticipatory state anxiety in the scanning context may cause children with moderate and high trait anxiety to be hypervigilant to threats, further compounding the effects of trait anxiety. Neuroimaging researchers should control for state anxiety so that systematic differences in brain activation resulting from MRI apprehension are not misleadingly attributed to demographic or environmental characteristics.

Using multiparametric Magnetic Resonance Imaging and Prostate Specific Membrane Antigen Positron Emission Tomography to detect and delineate the gross tumour volume of intraprostatic lesions - A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Radiation therapy is used frequently for patients with prostate cancer. Dose escalation to intraprostatic lesions (IPLs) has been shown to improve oncologic outcomes, without increasing toxicity. Both multiparametric MRI (mpMRI) and PSMA PET can be used to identify IPLs. MATERIALS AND METHODS: A systematic review was conducted to determine the ability of mpMRI, PSMA PET and their combination to detect IPLs prior to radical prostatectomy (RP) as correlated with the histology. Trials included patients that had mpMRI, PSMA PET, or both, prior to RP. The quality of the histopathological-radiological co-registration was assessed as high or low for each study. Recorded outcomes include sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). A meta-analysis was conducted using a bivariate model to determine the pooled sensitivity and specificity for each imaging modality. This systematic review was registered through PROSPERO (CRD42023389092). RESULTS: Altogether, 42 studies were included in the systematic review. Of these, 20 could be included in the meta-analysis. The pooled sensitivity (95 % CI), specificity (95 % CI) and AUROC for mpMRI (n = 13 studies) were 64.7 % (50.2 % - 76.9 %), 86.4 % (79.7 % - 91.1 %), and 0.852; the pooled outcomes for PSMA PET (n = 12) were 75.7 % (64.0 % - 84.5 %), 87.1 % (80.2 % - 91.9 %), and 0.889; for their combination (n = 5), the pooled outcomes were 70.3 % (64.1 % - 75.9 %), 81.9 % (71.9 % - 88.8 %), and 0.796. When reviewing studies with a high-quality histopathological-radiological co-registration, IPL delineation recommendations varied by study and the imaging modality used. CONCLUSION: All of mpMRI, PSMA PET or their combination were found to have very good diagnostic outcomes for detecting IPLs. Recommendations for delineating IPLs varied based on the imaging modalities used and between research groups. Consensus guidelines for IPL delineation would help with creating consistency for focal boost radiation treatments in future studies.

Multitask learning for predicting pulmonary absorption of chemicals.

Pulmonary absorption is an important route for drug delivery and chemical exposure. To streamline the chemical assessment process for the reduction of animal experiments, several animal-free models were developed for pulmonary absorption research. While Calu-3 and Caco-2 cells and their derived computational models were used in estimating pulmonary permeability, the ex vivo isolated perfused lung (IPL) models are considered more clinically relevant measurements. However, the IPL experiments are resource-consuming making it infeasible for the large-scale screening of potential inhaled toxicants and drugs. In silico models are desirable for estimating pulmonary absorption. This study presented a novel machine learning method that employed an extratrees-based multitask learning approach to predict the IPL absorption rate constant (kaIPL) of various chemicals. The shared permeability knowledge was extracted by simultaneously learning three relevant tasks of Caco-2 and Calu-3 cell permeability and IPL absorption rate. Seven informative physicochemical descriptors were identified. A rigorous evaluation of the developed prediction model showed good performance with a high correlation between predictions and observations (r = 0.84) in the independent test dataset. Two case studies of inhalation drugs and respiratory sensitizers revealed the potential application of this model, which may serve as a valuable tool for predicting pulmonary absorption of chemicals.

Treatment of ocular rosacea: a systematic review.

Rosacea is a common chronic skin disease distributed primarily around the central face. Ocular manifestations of rosacea are poorly studied, and estimates of prevalence vary widely, ranging from 6% to 72% in the rosacea population. Treatment options for ocular rosacea include lid hygiene, topical and oral antibiotics, cyclosporine ophthalmic emulsion, oral vitamin A derivatives, and intense pulsed light; however, a direct comparison of treatment methods for ocular rosacea is lacking. This review aims to compare treatment efficacy and adverse events for different treatment modalities in ocular rosacea. We performed a systematic review by searching Cochrane, MEDLINE and Embase. Title, abstract, full text screening, and data extraction were done in duplicate. Sixty-six articles met the inclusion criteria, representing a total of 1,275 patients. The most effective treatment modalities were topical antimicrobials and oral antibiotics, which achieved complete or partial response in 91% (n = 82/90) and 89% (n = 525/580) of patients respectively, followed by intense pulsed light (89%, n = 97/109 partial response), cyclosporine ophthalmic emulsion (87% n = 40/46), and lid hygiene (65%, n = 67/105). Combination treatments achieved a complete or partial response in 90% (n = 69/77). Results suggest that topical antimicrobials, oral antibiotics, intense pulsed light. and cyclosporine were the most efficacious single modality treatments.

The Emerging Role of Visible Light in Melanocyte Biology and Skin Pigmentary Disorders: Friend or Foe?

Electromagnetic radiation, notably visible light (VL), has complicated effects on human skin, particularly pigmentation, which have been largely overlooked. In this review, we discuss the photobiological mechanisms, pathological effects, clinical applications and therapeutic strategies of VL at varying wavelengths on melanocyte biology and skin pigmentary disorders. Different VL wavelengths may impose positive or negative effects, depending on their interactions with specific chromophores, photoaging, ROS production, circadian rhythm and other photon-mediated reactions. Further in vivo and in vitro studies are required to establish the pathologic mechanisms and application principles of VL in pigmentary disorders, as well as optimal photoprotection with coverage against VL wavelengths.

Is It Possible for Light-Based Hair Removal Home Devices to Induce Ocular Damage? Systematic Review.

Light-based hair removal home devices emit intense pulse light (IPL) or Diode laser. While the Food and Drug Administration controls them in the US, Europe continues to classify them as cosmetic products. Emerging concerns are: what if an unprotected eye is inadvertently exposed to light emission? Or if the consumer tries to overcome the protective safety features? We performed this systematic review by searching the Medline, CENTRAL, and Google Scholar databases to investigate the ocular damage reported after exposure to IPL for hair removal. We could not identify any case reported following exposure to home devices; however, a total of 20 patients were identified with iris atrophy, anterior chamber inflammation, and/or retinal pigment epithelium damage following exposure to office IPL or Diode lights. 40% were not using any protective eyewear during the light procedure. The reported fluences were in the range of 20-24 J/cm2. Although the ocular damage was identified following office devices, the reported fluences were within the home device's limits. For that, manufacturers should provide clear instructions on the package regarding the ocular hazards, the importance of using protective goggles, and a firm warning not to overcome the contact sensors. Home device-induced ocular damage is still a concern, perhaps under-reported.

Central macular morphology and optic nerve fibre layer thickness in young adults born premature and screened for retinopathy of prematurity.

PURPOSE: To investigate central retinal morphology and optic retinal nerve fibre layer (RNFL) in prematurely born young adults and compare to term born controls. MATERIALS AND METHODS: The participants were 59 prematurely born individuals, with a birthweight ≤1.500 g, and 44 term born controls, all 25-29 years of age. Visual acuity (VA) and contrast sensitivity (CS) were assessed. The retinal macular thickness, ganglion cell-inner plexiform layer (GC-IPL) thickness and RNFL thickness were assessed with Cirrus optical coherence tomography (OCT). RESULTS: Central macular thickness was increased (mean 26.7 µm) in prematurely born individuals compared to controls. The macular GC-IPL was thinner (mean 3.84 µm), also when excluding those with previous retinopathy of prematurity (ROP) and those with neurological complications. Gestational age at birth and previous treatment of ROP were risk factors for a thicker macula, however, not for reduced GC-IPL. The average peripapillary RNFL was thinner (mean 4.61 µm) in the prematurely born individuals, also when excluding those with previous ROP and/or neurological complications. Within the prematurely born group, treated ROP was correlated with increased average RNFL. Further, both better VA and CS were associated with thinner optic nerve RNFL and thicker average GC-IPL. CONCLUSION: Macular and optic nerve morphology were influenced by premature birth as assessed with OCT in adult individuals. Gestational age at birth and treatment for ROP seemed to affect central macular thickness, and treated ROP affected the peripapillary RNFL. Thus, retinal sequelae remained in adulthood.

Amitriptyline inhibits bronchoconstriction and directly promotes dilatation of the airways.

INTRODUCTION: The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß2-sympathomimetics) and, depending on the severity of disease, additional long-term treatment (including inhaled glucocorticoids, long-acting ß2-sympathomimetics, anticholinergics, anti-IL-4R antibodies). The antidepressant amitriptyline has been identified as a relevant down-regulator of immunological TH2-phenotype in asthma, acting-at least partially-through inhibition of acid sphingomyelinase (ASM), an enzyme involved in sphingolipid metabolism. Here, we investigated the non-immunological role of amitriptyline on acute bronchoconstriction, a main feature of airway hyperresponsiveness in asthmatic disease. METHODS: After stimulation of precision cut lung slices (PCLS) from mice (wildtype and ASM-knockout), rats, guinea pigs and human lungs with mediators of bronchoconstriction (endogenous and exogenous acetylcholine, methacholine, serotonin, endothelin, histamine, thromboxane-receptor agonist U46619 and leukotriene LTD4, airway area was monitored in the absence of or with rising concentrations of amitriptyline. Airway dilatation was also investigated in rat PCLS by prior contraction induced by methacholine. As bronchodilators for maximal relaxation, we used IBMX (PDE inhibitor) and salbutamol (ß2-adrenergic agonist) and compared these effects with the impact of amitriptyline treatment. Isolated perfused lungs (IPL) of wildtype mice were treated with amitriptyline, administered via the vascular system (perfusate) or intratracheally as an inhalation. To this end, amitriptyline was nebulized via pariboy in-vivo and mice were ventilated with the flexiVent setup immediately after inhalation of amitriptyline with monitoring of lung function. RESULTS: Our results show amitriptyline to be a potential inhibitor of bronchoconstriction, induced by exogenous or endogenous (EFS) acetylcholine, serotonin and histamine, in PCLS from various species. The effects of endothelin, thromboxane and leukotrienes could not be blocked. In acute bronchoconstriction, amitriptyline seems to act ASM-independent, because ASM-deficiency (Smdp1-/-) did not change the effect of acetylcholine on airway contraction. Systemic as well as inhaled amitriptyline ameliorated the resistance of IPL after acetylcholine provocation. With the flexiVent setup, we demonstrated that the acetylcholine-induced rise in central and tissue resistance was much more marked in untreated animals than in amitriptyline-treated ones. Additionally, we provide clear evidence that amitriptyline dilatates pre-contracted airways as effectively as a combination of typical bronchodilators such as IBMX and salbutamol. CONCLUSION: Amitriptyline is a drug of high potential, which inhibits acute bronchoconstriction and induces bronchodilatation in pre-contracted airways. It could be one of the first therapeutic agents in asthmatic disease to have powerful effects on the TH2-allergic phenotype and on acute airway hyperresponsiveness with bronchoconstriction, especially when inhaled.

The use of carbon dioxide and intense pulsed light laser for the treatment of hypertrophic burn scars: A case series.

Introduction: Hypertrophic scarring is a common and debilitating consequence of burn scars. While there is limited evidence for current treatment options, laser therapy has been shown to be effective, low risk and minimally invasive. This study assesses the use of carbon dioxide lasers and intense pulsed light devices in the treatment of hypertrophic burn scars. Methods: In this case series, patients were recruited from a hypertrophic burn scar waitlist and completed a Patient and Observer Scar Assessment Scale prior to and six weeks after laser therapy. The Nordlys (intense pulsed light) and CO2RE (carbon dioxide) systems from Candela Medical were used, with a range of settings used depending on the assessment of the burn scar. The differences between scores were calculated for the total Patient and Observer Scar Assessment Scale score, pain, itch, colour, stiffness, thickness, irregularity and the overall opinion of the scar. Statistical analysis was completed using a paired, two-tailed student T test. Results: A total of 31 patients were recruited for this trial with a range of scar locations, surface areas and mechanism of burn injury. The calculated difference in mean showed a significant reduction for the overall Patient and Observer Scar Assessment Scale score (1.93, p < 0.0001), pain (1.39, p = 0.0002), itch (1.84, p = 0.0002), colour (1.97, p < 0.0001), stiffness (2.47, p < 0.0001), thickness (2.1, p < 0.0001), irregularity (1.89, p < 0.0001) and overall opinion (1.58, p = 0.0003). Conclusion: Current management options for hypertrophic scarring have limited evidence. Laser therapy presents a minimally invasive procedure that can be completed under topical anaesthetic and has shown to be effective following a single treatment of combined carbon dioxide laser and intense pulsed light device therapy. Lay Summary: Many people will suffer a burn injury throughout their life and up to almost 3 out of 4 people with burn injuries will suffer from hypertrophic scars (a thickened, red and itchy scar). These scars cause distress both due to their appearance and their reduction of function, particularly over a joint or muscle. Laser therapy, in which different wave lengths of light (pulsed light) or gas (carbon dioxide) target the scar, has been found to be effective and have minimal side effects in the management of hypertrophic scars. While individual lasers have been assessed and found to be effective and low risk, the combined use of multiple lasers on the same scar has not been extensively studied. We studied the effectiveness of both light and gas laser therapies on hypertrophic scars. Patients with hypertrophic scars completed a questionnaire that focused on their perspective of their scar (pain, itch, stiffness, thickness, irregularity, overall opinion) prior to the treatment. The patients then underwent laser therapy (with local anaesthetic gel) with either pulsed light and/or carbon dioxide (gas) laser. The type of laser used was decided by the clinician performing the therapy depending on scar location and thickness. Patients then re-completed the subjective survey six weeks following the laser therapy, and the results compared. We learnt that laser therapy (both light, gas and a combination of both) are effective (and low risk) in reducing the subjective burden of the scar for the patient.

Multi-Frequency RF Combined with Intense Pulsed Light Improves Signs and Symptoms of Dry Eye Disease Due to Meibomian Gland Dysfunction.

Purpose: To evaluate the efficacy of multi-frequency RF and IPL + MGX combination for treatment of Meibomian Gland Dysfunction (MGD). Patients and Methods: Eligible subjects had signs and moderate-to-severe symptoms of DED (Dry Eye Disease) due to MGD. Subjects underwent 4 treatments at 2-week intervals. Each treatment consisted of intense pulsed light (IPL) followed by radiofrequency (RF) on the periocular skin, followed by meibomian gland expression (MGX). The main outcome measure was the quality of meibum in 15 meibomian glands along the lower eyelid, using the modified Meibomian Gland Score (mMGS). The main hypothesis was a reduction of mMGS between the baseline (BL) and the follow-up (FU). Other outcome measures, such as symptoms measured with the OSDI (Ocular Surface Disease Index) questionnaire, meibography, non-invasive tear break-up time (NIBUT), and matrix metallopeptidase 9 (MMP-9) levels in tear samples were evaluated as well. Results: 31 subjects completed the FU. Between BL and FU, mMGS decreased from 30.4 (8.5) to 9.3 (9.5) (-69.3%, 95% CI: -55.6% to -82.9%, p<0.0001); OSDI decreased from 63.6 (17.2) to 25.0 (20.6) (-60.7%, 95% CI: -47.8% to -73.5%, p<0.0001); NIBUT did not change (p=0.92). An adjusted model with a historical control was constructed to allow the comparison of these subjects with those treated similarly with IPL+MGX (but without RF) in a different study. This analysis identified that the change in mMGS was larger when RF was included (-20.9 vs -18.3, adjusted p-value (p_adjusted) <0.05). The difference in OSDI change was not significant (-38.1 vs -25.5, p_adjusted = 0.196). Conclusion: Combination of multi-frequency RF and IPL+MGX improves signs and symptoms of MGD. In comparison to a historical control, improvements were generally larger. A randomized controlled study comparing the combination of RF and IPL+MGX with IPL+MGX alone is required to further elaborate the relative contribution of RF.

Chromosome biorientation requires Aurora B's spatial separation from its outer kinetochore substrates, but not its turnover at kinetochores.

For correct chromosome segregation in mitosis, sister kinetochores must interact with microtubules from opposite spindle poles (biorientation). For this, aberrant kinetochore-microtubule interaction must be resolved (error correction) by Aurora B kinase. Once biorientation is formed, tension is applied on kinetochore-microtubule interaction, stabilizing this interaction. The mechanism for this tension-dependent process has been debated. Here, we study how Aurora B localizations at different kinetochore sites affect the biorientation establishment and maintenance in budding yeast. Without the physiological Aurora B-INCENP recruitment mechanisms, engineered recruitment of Aurora B-INCENP to the inner kinetochore, but not to the outer kinetochore, prior to biorientation supports the subsequent biorientation establishment. Moreover, when the physiological Aurora B-INCENP recruitment mechanisms are present, an engineered Aurora B-INCENP recruitment to the outer kinetochore, but not to the inner kinetochore, during metaphase (after biorientation establishment) disrupts biorientation, which is dependent on the Aurora B kinase activity. These results suggest that the spatial separation of Aurora B from its outer kinetochore substrates is required to stabilize kinetochore-microtubule interaction when biorientation is formed and tension is applied on this interaction. Meanwhile, Aurora B exhibits dynamic turnover on the centromere/kinetochore during early mitosis, a process thought to be crucial for error correction and biorientation. However, using the engineered Aurora B-INCENP recruitment to the inner kinetochore, we demonstrate that, even without such a turnover, Aurora B-INCENP can efficiently support biorientation. Our study provides important insights into how Aurora B promotes error correction for biorientation in a tension-dependent manner.