Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness. METHODS: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas. RESULTS: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas. CONCLUSIONS: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement / Correlación entre hiperconectividad de la corteza auditiva antes del tratamiento con estimulación magnética transcraneal repetitiva y mejoría de los acúfenos

Introduction: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness. Methods: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas. Results: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas. Conclusions: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.(AU)

Introducción: La estimulación magnética transcraneal repetitiva (EMTr) se ha utilizado como posible tratamiento para los acúfenos, aunque su efectividad es variable e impredecible. Planteamos la hipótesis de que existe una correlación entre la conectividad funcional en estado de reposo antes de aplicar EMTr y la efectividad de dicho tratamiento. Métodos: Aplicamos EMTr a 1 Hz sobre la corteza auditiva primaria (A1) y la corteza prefrontal dorsolateral (CPFDL) izquierdas de 10 pacientes con acúfenos y 10 controles del mismo rango de edad. Se realizaron estudios de resonancia magnética funcional (RMF) en estado de reposo de todos los pacientes aproximadamente una semana antes de la EMTr. En cada caso, se construyó un mapa de conectividad basado en las ROIs, en el que las ROIs eran las áreas que se tratarían con la EMTr. Resultados: La región temporal superior izquierda mostró una conectividad positiva significativamente mayor con el área A1 izquierda y mayor conectividad negativa con la CPFDL izquierda en los pacientes con acúfenos que en los controles. Además, las áreas frontoparietal izquierda y cerebelar derecha mostraron una conectividad negativa significativamente superior con el área A1 izquierda y mayor conectividad positiva con la CPFDL izquierda. La hiperconectividad de las ROIs se correlacionó con mejoría de los acúfenos según las puntuaciones pre-EMTr y 2 semanas post-EMTr en la escala Tinnitus Handicap Inventory. La mejoría de los acúfenos se correlacionó de manera significativa con la hiperconectividad del área A1 izquierda; sin embargo, no se encontró correlación con la conectividad de la CPFDL izquierda. El resultado favorable del tratamiento con EMTr se asocia con una mayor conectividad positiva en áreas temporales superiores de ambos hemisferios y con mayor conectividad negativa en áreas frontales bilaterales...(AU)

Effect of supplementation of cryoprotectant solution with hydroxypropyl cellulose for vitrification of bovine oocytes.

BACKGROUND: Successful cryopreservation of bovine oocytes is very important for research and commercial applications. However, the survival and development rate of vitrified-thawed (VT) oocytes are lower than those of non-vitrified-thawed (non-VT) oocytes. OBJECTIVE: To investigate the effect of adding hydroxypropyl cellulose (HPC) to the vitrification solution for bovine oocytes. MATERIALS AND METHODS: For vitrification, bovine metaphase II oocytes were pretreated with a solution containing 10% ethylene glycol supplemented with 0, 10, 50, or 100 ug/mL HPC for 5 min, exposed to a solution containing 30% ethylene glycol supplemented with 0, 10, 50, or 100 ug/mL HPC for 30 s, and then directly plunged into liquid nitrogen. RESULTS: The survival rate of oocytes was significantly higher in the 50 HPC group than in the 0, 10, and 100 HPC groups. The reactive oxygen species level was lower in the non-VT and 50 HPC groups than in the other groups. The mRNA levels of proapoptotic genes (Bax) were lower in the non-VT, 0, and 50 HPC groups than in the other groups. The mRNA levels of antiapoptotic genes (BCl2) were higher in the non-VT than in the other groups. The development rates of embryos (day 8) obtained via parthenogenetic activation (PA) were determined in the non-VT, 0 HPC, and 50 HPC groups. The cleavage rate was significantly higher in the non-VT group. CONCLUSION: Supplementation of vitrification solution with HPC improves the survival of VT bovine oocytes and the development capacity of embryos derived from these oocytes via PA. doi.org/10.54680/fr23110110212.

Brillouin light scattering in niobium doped lead zirconate single crystal.

Brillouin light scattering experiments were performed for lead zirconate single crystals doped with niobium. Special attention was paid to the elastic mode softening near phase transition temperatures. The results are compared with data obtained by Raman light scattering experiments. We observed that the interaction between acoustic and optic modes is responsible for symmetry breaking far above TC, leading to polar regions' appearance. No changes in the acoustic mode frequency and its damping are observed at TC, where ε(T) exhibits a maximum value. The absence of these changes and the central peak observed in Raman experiments suggest that the phase transition at TC is mainly of the order-disorder type. The origin of other phase transitions is discussed as well.

Filtration performance and breathing resistance of elastomeric half mask respirator P100 filter cartridges after repeated and extended use in healthcare settings.

In 2020, the Centers for Disease Control and Prevention recommended the use of the National Institute for Occupational Safety and Health-certified Elastomeric Half Mask Respirators equipped with N95 or P100 respirator filter cartridges for protection against the SARS-CoV-2 viral agent, as a viable alternative to N95 filtering facepiece respirators. Additionally, the Centers for Disease Control and Prevention recommendations stated that based on current practice, it was acceptable to repeatedly use these filter cartridges for up to 12 months as a contingency capacity strategy during anticipated respirator shortages. To validate this recommendation, an investigation was undertaken in which Elastomeric Half Mask Respirators equipped with P100 respirator filter cartridges were deployed and used by healthcare professionals in clinical settings (i.e., inpatient nursing units, operating rooms) for extended periods. These filter cartridges were subsequently tested to accurately quantify their filtration efficiency and breathing resistance to determine if they continued to meet National Institute for Occupational Safety and Health's performance requirements. Findings from this investigation confirmed that an Elastomeric Half Mask Respirator when equipped with a P100 filter cartridge continues to provide a high level of aerosol filtration performance (≥99.97%) and exhibits little change in breathing resistance even after 12 months of repeated use (i.e., wear, cleaning, and disinfection between patient use and at the end of work shift) in healthcare settings.

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness. METHODS: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas. RESULTS: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas. CONCLUSIONS: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.

Targeting NLRP3 Inflammasome Reduces Age-Related Experimental Alveolar Bone Loss.

The cause of chronic inflammatory periodontitis, which leads to the destruction of periodontal ligament and alveolar bone, is multifactorial. An increasing number of studies have shown the clinical significance of NLRP3-mediated low-grade inflammation in degenerative disorders, but its causal linkage to age-related periodontitis has not yet been elucidated. In this study, we investigated the involvement of the NLRP3 inflammasome and the therapeutic potential of NLRP3 inhibition in age-related alveolar bone loss by using in vivo and in vitro models. The poor quality of alveolar bones in aged mice was correlated with caspase-1 activation by macrophages and elevated levels of IL-1ß, which are mainly regulated by the NLRP3 inflammasome, in periodontal ligament and serum, respectively. Aged mice lacking Nlrp3 showed better bone mass than age-matched wild-type mice via a way that affects bone resorption rather than bone formation. In line with this finding, treatment with MCC950, a potent inhibitor of the NLRP3 inflammasome, significantly suppressed alveolar bone loss with reduced caspase-1 activation in aged mice but not in young mice. In addition, our in vitro studies showed that the addition of IL-1ß encourages RANKL-induced osteoclastogenesis from bone marrow-derived macrophages and that treatment with MCC950 significantly suppresses osteoclastic differentiation directly, irrelevant to the inhibition of IL-1ß production. Our results suggest that the NLRP3 inflammasome is a critical mediator in age-related alveolar bone loss and that targeting the NLRP3 inflammasome could be a novel option for controlling periodontal degenerative changes with age.

TLR5 activation induces expression of the pro-inflammatory mediator Urokinase Plasminogen Activator via NF-κB and MAPK signalling pathways in human dental pulp cells.

AIM: To explore the involvement of TLR5 in pulp inflammation and to examine the effects of TLR5 activation with its ligand, FlaB protein, on pro-inflammatory gene expression. METHODOLOGY: TLR5 expression in dental pulp tissues and human dental pulp cells (hDPCs) were determined by immunohistochemistry, immunocytochemistry, Western blots and RT-PCR analyses. To examine the role of TLR5, hDPCs were treated with recombinant FlaB protein (500 ng mL-1 ) to activate the receptor or with a small interfering RNA against TLR5 (si-TLR5) to downregulate the receptor. After exposure to FlaB, the expression of inflammation-related proteins was screened using a protein array kit. Western blots or qRT-PCR analyses were performed to identify changes in the expression of uPA (urokinase plasminogen activator), TIMPs (tissue inhibitor of metalloproteinases), and IL-6 and to determine their signalling pathways. Statistical analysis was performed using one-way analysis of variance (anova) with Tukey post hoc test; P < 0.05 was considered statistically significant. RESULT: TLR5 expression was identified in pulp tissues and hDPCs. In the protein array analysis, treatment with FlaB significantly increased uPA expression (P < 0.01) and significantly decreased TIMP1/4 (P < 0.05). FlaB treatment also significantly increased expression of the inflammatory marker IL-6 (P < 0.01). FlaB treatment increased phosphorylation of the NF-κB p65 subunit, JNK, p38 and ERK. Chemical inhibitors of NF-κB (Bay11-7082), p38 (SB202190) or ERK (U0126) decreased the FlaB induction of uPA expression. Downregulation of TLR5 expression by siRNA decreased the FlaB induction of uPA protein and p65 phosphorylation. CONCLUSION: TLR5 activation with FlaB treatment induced the expression of uPA via the NF-κB and MAPK signalling pathways. Flagellin-bearing oral bacteria may cause pulp inflammation through TLR5. The findings provide new clues to control pulpal diseases by targeting TLR5 signalling pathways.

Strong magnetoelectric coupling in mixed ferrimagnetic-multiferroic phases of a double perovskite.

Exploring new magnetic materials is essential for finding advantageous functional properties such as magnetoresistance, magnetocaloric effect, spintronic functionality, and multiferroicity. Versatile classes of double perovskite compounds have been recently investigated because of intriguing physical properties arising from the proper combination of several magnetic ions. In this study, it is observed that the dominant ferrimagnetic phase is coexisted with a minor multiferroic phase in single-crystalline double-perovskite Er2CoMnO6. The majority portion of the ferrimagnetic order is activated by the long-range order of Er3+ moments below TEr = 10 K in addition to the ferromagnetic order of Co2+ and Mn4+ moments arising at TC = 67 K, characterized by compensated magnetization at TComp = 3.15 K. The inverted magnetic hysteresis loop observed below TComp can be described by an extended Stoner-Wohlfarth model. The additional multiferroic phase is identified by the ferroelectric polarization of ~0.9 µC/m2 at 2 K. The coexisting ferrimagnetic and multiferroic phases appear to be strongly correlated in that metamagnetic and ferroelectric transitions occur simultaneously. The results based on intricate magnetic correlations and phases in Er2CoMnO6 enrich fundamental and applied research on magnetic materials through the scope of distinct magnetic characteristics in double perovskites.

Direct observation of a two-dimensional hole gas at oxide interfaces.

The discovery of a two-dimensional electron gas (2DEG) at the LaAlO3/SrTiO3 interface 1 has resulted in the observation of many properties2-5 not present in conventional semiconductor heterostructures, and so become a focal point for device applications6-8. Its counterpart, the two-dimensional hole gas (2DHG), is expected to complement the 2DEG. However, although the 2DEG has been widely observed 9 , the 2DHG has proved elusive. Herein we demonstrate a highly mobile 2DHG in epitaxially grown SrTiO3/LaAlO3/SrTiO3 heterostructures. Using electrical transport measurements and in-line electron holography, we provide direct evidence of a 2DHG that coexists with a 2DEG at complementary heterointerfaces in the same structure. First-principles calculations, coherent Bragg rod analysis and depth-resolved cathodoluminescence spectroscopy consistently support our finding that to eliminate ionic point defects is key to realizing a 2DHG. The coexistence of a 2DEG and a 2DHG in a single oxide heterostructure provides a platform for the exciting physics of confined electron-hole systems and for developing applications.

The MLL recombinome of acute leukemias in 2017.

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.

Simultaneous Subtotal Pancreatectomy and Streptozotocin Injection for Diabetes Modeling in Cynomolgus Monkeys.

BACKGROUND: In an experimental animal model of islet transplantation, stable induction of insulin-dependent diabetes mellitus (IDDM) and islet isolation from donor pancreas are essential. Total pancreatectomy for IDDM induction and islet procurement in nonhuman primates leads to unwanted loss of exocrine function and may lead to morbidities associated with IDDM. METHODS: IDDM induction with streptozotocin (STZ) is associated with drug toxicity of STZ and necessitates the killing of another animal for islet procurement. In this study, we performed a subtotal pancreatectomy combined with reduced STZ injection to induce IDDM and procure islets in a nonhuman primate model. RESULTS: Twelve cynomolgus monkeys received low-dose STZ injections (60 mg/kg) simultaneously with subtotal pancreatectomy. All monkeys recovered from the procedure without complications. IDDM was induced in the animals. 57,691 ± 16,050 islets were isolated from the resected pancreas and transplanted into other monkeys. CONCLUSIONS: Simultaneous subtotal pancreatectomy and low-dose STZ injection represent an effective and safe method to create an animal model of insulin dependence diabetes, while at the same time providing sufficient amounts of fresh islet cells for allotransplantation without requiring killing of additional animals.

High-intensity focused ultrasound treatment for skin: ex vivo evaluation.

BACKGROUND/PURPOSE: High-intensity focused ultrasound (HIFU) has been used for skin tightening. However, there is a rising concern of irreversible adverse effects. Our aim was to evaluate the depth of thermal injury zone after HIFU energy passes through different condition. MATERIALS AND METHODS: To analyze the consistency of the HIFU device, phantom tests were performed. Simulations were performed on ex vivo porcine tissues to estimate the area of the thermal coagulation point (TCP) according to the applied energy and skin condition. The experiment was designed in three orientations: normal direction (from epidermis to fascia), reverse direction (from fascia to epidermis), and normal direction without epidermis. RESULTS: The TCP was larger and wider depending on the applied fluence and handpieces (HPs). When we measured TCP in different directions, the measured area in the normal direction was more superficially located than that in the reverse direction. The depth of the TCP in the porcine skin without epidermis was detected at 130% deeper than in skin with an intact epidermis. CONCLUSION: The affected area by HIFU is dependent on the skin condition and the characteristics of the HP and applied fluence. Considerations of these factors may be the key to minimize the unwanted adverse effects.

Impact of high-mobility group box 1 on melanocytic survival and its involvement in the pathogenesis of vitiligo.

BACKGROUND: Vitiligo is attributable to loss of functional melanocytes and is the most common acquired depigmenting disorder. Oxidative stress and intense ultraviolet irradiation are known to aggravate this condition. The nonhistone high-mobility group box 1 (HMGB1) DNA-binding protein is a physiological activator of immune responses, cellular proliferation and cell death. Although it is implicated in the pathogenesis of autoimmune diseases and cutaneous disorders, the precise role of HMGB1 in melanocytes has yet to be studied. OBJECTIVES: To elucidate the effect of HMGB1 on melanocytic survival and its involvement in the pathogenesis of vitiligo. METHODS: Melanocytes were treated with recombinant HMGB1 (rHMGB1). Thereafter, apoptosis-, autophagy- and melanogenesis-related molecules were detected. Ex vivo skin organ culture was performed after rHMGB1 treatment. Also, levels of HMGB1 were examined in blood and skin specimens from patients with vitiligo. RESULTS: In this study, rHMGB1 increased expression of cleaved caspase 3 and decreased melanin production and expression of melanogenesis-related molecules. rHMGB1-induced caspase 3 activation was confirmed through preincubation with a pan-caspase inhibitor. In ex vivo experiments for the confirmation of HMGB1-induced melanocyte apoptosis, melanocyte disappearance and increased caspase 3 activation were observed in rHMGB1-treated skin tissues. In Western blot analysis and enzyme-linked immunosorbent assay, patients with active vitiligo showed significantly higher blood levels of HMGB1 (vs. healthy controls). Also, greater expression of HMGB1 was observed in vitiliginous skin (vs. uninvolved skin). CONCLUSIONS: External stimuli (e.g. oxidative stress and ultraviolet irradiation) may trigger HMGB1 release by keratinocytes, thereby perpetuating vitiligo through HMGB1-induced melanocytic apoptosis.