Treatment-induced Improvement Research Articles

Uncovering the chemical bonding basis for ultrasound treatment-induced improvement in the molecular flexibility of myofibrillar proteins from low-salt meat batters with added methylcellulose

Ultrasound (US) treatment modifies the construction of myofibrillar proteins (MPs) to improve the properties of low-salt meat batters (LMTs) with added methylcellulose (MC). This study investigated the correlation between the construction of MPs and their flexibility in LMTs adding different MC levels with US treatment. MPs exhibited the highest flexibility at 100 W, owing to a high concentration of myosin with hydrophobic interaction contents, e.g. 5.98 mg/mL in MPs from LMTs adding 0.4% MC. However, the ionic and disulfide bonds were reversed. SDS-PAGE revealed the depolymerization of MPs at low power (<100 W), whereas macromolecular aggregates were produced as the cross-linking of MPs at ≥100 W. This phenomenon is supported by the chemical bonding and flexibility of proteins. These findings demonstrate that appropriate US treatment induces the flexibility alteration of MPs from LMTs with added MC by modifying their construction and regulating bond interactions.

Structural Neuroplasticity Effects of Singing in Chronic Aphasia.

Singing-based treatments of aphasia can improve language outcomes, but the neural benefits of group-based singing in aphasia are unknown. Here, we set out to determine the structural neuroplasticity changes underpinning group-based singing-induced treatment effects in chronic aphasia. Twenty-eight patients with at least mild nonfluent poststroke aphasia were randomized into two groups that received a 4-month multicomponent singing intervention (singing group) or standard care (control group). High-resolution T1 images and multishell diffusion-weighted MRI data were collected in two time points (baseline/5 months). Structural gray matter (GM) and white matter (WM) neuroplasticity changes were assessed using language network region of interest-based voxel-based morphometry (VBM) and quantitative anisotropy-based connectometry, and their associations to improved language outcomes (Western Aphasia Battery Naming and Repetition) were evaluated. Connectometry analyses showed that the singing group enhanced structural WM connectivity in the left arcuate fasciculus (AF) and corpus callosum as well as in the frontal aslant tract (FAT), superior longitudinal fasciculus, and corticostriatal tract bilaterally compared with the control group. Moreover, in VBM, the singing group showed GM volume increase in the left inferior frontal cortex (Brodmann area 44) compared with the control group. The neuroplasticity effects in the left BA44, AF, and FAT correlated with improved naming abilities after the intervention. These findings suggest that in the poststroke aphasia group, singing can bring about structural neuroplasticity changes in left frontal language areas and in bilateral language pathways, which underpin treatment-induced improvement in speech production.

Uncovering the rheological properties basis for freeze drying treatment-induced improvement in the solubility of myofibrillar proteins

Myofibrillar proteins (MPs) are an important nutritional supplement and have great significance in sports training and rehabilitation therapy. Currently, MPs preservation is still disputed since they are vulnerable to degradation, polymerization, and denaturation. Freeze-drying is an emerging technology for protein preservation, its effects on the functionality of MPs from different sources have not yet been thoroughly studied. This study aims to evaluate the performance differences of freeze-drying in maintaining the functional characteristics of MPs from fish and mammalian sources, providing valuable insights for the processing and preservation of MPs, and providing nutritional support for nursing and rehabilitation. The results showed that freeze-drying was an efficient method for protein preservation, and the effects of freeze-drying on both fish and mammalian sources MPs were significant (p < 0.05) consistent. Specifically, whether before and after freeze-drying, the solubility of fish MPs (FMPs) was significant (p < 0.05) lower than that of mammalian MPs, while the foaming and emulsifying properties were significant (p < 0.05) higher than those of beef and sheep MPs (BMPs and SMPs, respectively). Furthermore, the most efficient protein concentration for freeze-drying was 10 mg/mL, and with this concentration, the gel strengths of BMPs and SMPs showed an insignificant difference (p > 0.05) after freeze-drying.

Inverse psoriasis: the diagnostic value of dermatoscopic assessment and the experience of treatment with a combination topical agent (a clinical series)

Background: Inverse psoriasis that is characterized by skinfold rash is seen in 12 to 36% of European patients with psoriasis. Isolated involvement of skinfolds can mimic a number of dermatoses with similar location. The differential diagnosis is increasingly frequently based on non-invasive methods, including dermatoscopy. Taking into account the warm and wet milieu of skinfolds, facilitating secondary infection, topical antibacterials and antiseptics are recommended for treatment, along with topical glucocorticosteroids and vitamin D3 analogues.&#x0D; Materials and methods: We have analyzed the results of assessment and treatment of 15 patients with psoriasis of major skinfolds that were admitted to the in-patient department of dermatology. All patients underwent dermatoscopy at 20 magnification. The patients were treated with desensitizing agents, hepatic protectors, and group B vitamins. Topical treatments applied in the rash areas included a combination topical agent containing mometasone furoate (0.5 mg), gentamicin sulfate (1 mg), econazole nitrate (10 mg), and dexpanthenol (50 mg). The treatment was considered effective if the M-PASI decreased at least by 75%; the results were assessed after 7 and 14 days of treatment.&#x0D; Results: In all cases, dermatoscopy of the vulgar psoriasis lesions showed vermilion or red to rosy background with evenly distributed dotted vessels and white scales diffusely located all over the visualized surface. The skinfold lesions were characterized by rosy or red background with evenly distributed dotted vessels, white scales located either as isolated groups, or at the periphery of the visualized areas; some plaques had local erosions, and in one case, hemorrhages. Morphological assessment of the biopsy samples in all patients with isolated skinfold lesions (n = 5) confirmed the diagnosis of psoriasis. Treatment-induced improvement was seen at day 2 to 3, and at day 14, there was a decrease of M-PASI by 90% in 6 (40%) patients and resolution of the lesions in 9 (60%). There were no treatment-associated adverse events or reactions.&#x0D; Conclusion: Dermatoscopy has proved to be a useful tool for non-invasive diagnostics of inverse psoriasis. At low magnification ( 20), its main sign was an even distribution of dotted vessels throughout the visualized area. In a number of cases, the dermatoscopic symptoms additionally included white scales grouped as isolated foci. The addition of the combination topical agent (mometasone furoate, gentamicin sulfate, econazole nitrate, and dexpanthenol) to the standard systemic therapy facilitated almost full resolution of skinfold psoriatic lesions.

Monitoring Neuronal Network Disturbances of Brain Diseases: A Preclinical MRI Approach in the Rodent Brain.

Functional and structural neuronal networks, as recorded by resting-state functional MRI and diffusion MRI-based tractography, gain increasing attention as data driven whole brain imaging methods not limited to the foci of the primary pathology or the known key affected regions but permitting to characterize the entire network response of the brain after disease or injury. Their connectome contents thus provide information on distal brain areas, directly or indirectly affected by and interacting with the primary pathological event or affected regions. From such information, a better understanding of the dynamics of disease progression is expected. Furthermore, observation of the brain's spontaneous or treatment-induced improvement will contribute to unravel the underlying mechanisms of plasticity and recovery across the whole-brain networks. In the present review, we discuss the values of functional and structural network information derived from systematic and controlled experimentation using clinically relevant animal models. We focus on rodent models of the cerebral diseases with high impact on social burdens, namely, neurodegeneration, and stroke.

Improvement of polymer electrolyte fuel cell performance by gas diffusion layer with relatively hydrophilic surface

To improve the performance of polymer electrolyte fuel cells under high current density operation, the flooding problem in gas diffusion layers (GDLs) should be solved. In this study, a novel GDL with a relatively hydrophilic surface, consisting of hydrophilic and hydrophobic pores, which yielded a wettability distribution in the thickness direction, was proposed to achieve smooth water transport. First, we fabricated GDLs with surfaces partially hydrophilized by Nafion, and we demonstrated that the cell performance improved with this treatment. Cell performance tests suggest that a GDL with optimized surface treatment could reduce the water accumulation compared with the hydrophobic GDL used in this study; it could also improve cell performance owing to low mass transport losses. To verify the surface treatment-induced improvement in the oxygen diffusivity of the GDL, the water transport in the GDL was simulated using a lattice Boltzmann method. The results showed that the water accumulation in the GDL with surface treatment was small because the water flow was limited to the thin relatively hydrophilic region. Consequently, the oxygen diffusivity was higher than that of the hydrophobic GDL. Therefore, the flooding problem can be suppressed by the surface treatment, which yields a relatively hydrophilic surface.

Treatment With CD52 Antibody Protects Neurons in Experimental Autoimmune Encephalomyelitis Mice During the Recovering Phase.

Multiple sclerosis (MS) is a chronic autoimmune disease driven by T and B lymphocytes. The remyelination failure and neurodegeneration results in permanent clinical disability in MS patients. A desirable therapy should not only modulate the immune system, but also promote neuroprotection and remyelination. To investigate the neuroprotective effect of CD52 antibody in MS, both C57BL/6J and SJL mice with experimental autoimmune encephalomyelitis (EAE) were treated with CD52 antibody at the peak of disease. Treatment with CD52 antibody depleted T but not B lymphocytes in the blood, reduced the infiltration of T lymphocytes and microglia/macrophages in the spinal cord. Anti-CD52 therapy attenuated EAE scores during the recovery phase. It protected neurons immediately after treatment (within 4 days) as shown by reducing the accumulation of amyloid precursor proteins. It potentially promoted remyelination as it increased the number of olig2/CC-1-positive mature oligodendrocytes and prevented myelin loss in the following days (e.g., 14 days post treatment). In further experiments, EAE mice with a conditional knockout of BDNF in neurons were administered with CD52 antibodies. Neuronal deficiency of BDNF attenuated the effect of anti-CD52 treatment on reducing EAE scores and inflammatory infiltration but did not affect anti-CD52 treatment-induced improvement of myelin coverage in the spinal cord. In summary, anti-CD52 therapy depletes CD4-positive T lymphocytes, prevents myelin loss and protects neurons in EAE mice. Neuronal BDNF regulates neuroprotective and anti-inflammatory effect of CD52 antibody in EAE mice.

Clinical and Neural Predictors of Treatment Response to Music Listening Intervention after Stroke.

Patients with post-stroke impairments present often significant variation in response to therapeutic interventions. Recent studies have shown that daily music listening can aid post-stroke recovery of language and memory, but reliable predictors of treatment response are unknown. Utilizing data from the music intervention arms of a single-blind randomized controlled trial (RCT) on stroke patients (N = 31), we built regression models to predict the treatment response of a two-month music listening intervention on language skills and verbal memory with baseline demographic, clinical and musical data as well as fMRI data from a music listening task. Clinically, greater improvement in verbal memory and language skills after the music listening intervention were predicted by the severity of the initial deficit and educational level. Neurally, greater baseline fMRI activation during vocal music listening in the left parietal cortical and medial frontal areas predicted greater treatment-induced improvement in language skills and greater baseline engagement of the auditory network during instrumental music listening predicted improvement in both verbal memory and language skills. Our results suggest that clinical, demographic, and neuroimaging data predicts music listening treatment response. This data could be used clinically to target music-based treatments.

The impact of levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in men with autoimmune hypothyroidism and early-onset androgenetic alopecia.

Administration of testosterone or dehydroepiandrosterone to subjects with low levels of these hormones was found to reduce thyroid antibody titres. Male-pattern baldness is accompanied by mildly increased androgen levels. The present study was aimed at investigating whether early-onset androgenetic alopecia determines the impact of exogenous levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in young men with autoimmune hypothyroidism. The study included 2 thyroid-antibody-matched groups of men with autoimmune hypothyroidism: subjects with early-onset androgenetic alopecia (group 1; n = 24) and subjects with no evidence of hair loss (group 2; n = 24). All patients were treated with exogenous levothyroxine. Circulating titres of thyroid peroxidase and thyroglobulin antibodies, as well as levels of thyrotropin, free thyroxine, free triiodothyronine, prolactin, total testosterone, calculated bioavailable testosterone, dehydroepiandrosterone-sulphate, and oestradiol were measured before levothyroxine treatment and 6 months later. In both study groups, levothyroxine decreased thyroid antibody titres, reduced thyrotropin levels and increased free thyroid hormone levels. However, these effects were less pronounced in the men with early-onset male-pattern baldness than in the control men. The degree of reduction in antibody titres and thyrotropin levels correlated with baseline levels of total and calculated bioavailable testosterone, as well with baseline insulin sensitivity and treatment-induced improvement in insulin sensitivity. Concentrations of the remaining variables remained unchanged throughout the study period. The results of the current study suggest that the benefits of levothyroxine therapy in men with autoimmune hypothyroidism are less pronounced in individuals with early-onset androgenetic alopecia.

Cortical microstructural changes associated with treated aphasia recovery

ObjectivesTo investigate the hypothesis that language recovery in post‐stroke aphasia is associated with structural brain changes.MethodsWe evaluated whether treatment‐induced improvement in naming is associated with reorganization of tissue microstructure within residual cortical regions. To this end, we performed a retrospective longitudinal treatment study using comprehensive language‐linguistic assessments and diffusion MRI sequences optimized for the assessment of complex microstructure (diffusional kurtosis imaging) to evaluate the relationship between language treatment response and cortical changes in 26 individuals with chronic stroke‐induced aphasia. We employed elastic net statistical models controlling for baseline factors including age, sex, and time since the stroke, as well as lesion volume.ResultsWe observed that improved naming accuracy (Philadelphia Naming Test) was statistically associated with increased post‐treatment microstructural integrity in the left posterior superior temporal gyrus. Moreover, increase in microstructural integrity in the left middle temporal gyrus and left inferior temporal gyrus was specifically associated with a decrease in semantic paraphasias. This longitudinal relationship between brain tissue integrity and language improvement was not observed in other non‐language related brain regions.InterpretationOur findings provide evidence that structural brain changes in the preserved left hemisphere regions are associated with treatment‐induced language recovery in aphasia and are part of the mechanisms supporting language and brain injury recovery.

Novel mechanisms underlying anti-polycystic ovary like syndrome effects of electroacupuncture in rats: suppressing SREBP1 to mitigate insulin resistance, mitochondrial dysfunction and oxidative stress

BackgroundAcupuncture, a therapy of traditional Chinese medicine, is confirmed to exert the therapeutic action on polycystic ovary syndrome (PCOS). However, the detailed therapeutic mechanisms of acupuncture in PCOS remain ambiguous. In this study, we further investigated whether electroacupuncture (EA) alleviated PCOS-like symptoms in rats via regulating a metabolic regulator, sterol regulatory element binding protein-1 (SREBP1).MethodsThe PCOS-like rat model was built by hypodermic injection with dehydroepiandrosterone (DHEA). The rats were subjected to EA intervention (ST29 and SP6 acupuncture points) for 5 weeks. Primary granulosa cells were isolated from control and PCOS-like rats for evaluating insulin resistance, mitochondrial dysfunction and oxidative stress in vitro.ResultsThe expression of SREBP1 was increased in PCOS-like rats, which was suppressed by EA treatment. In addition, lentivirus-mediated overexpression of SREBP1 restrained EA treatment-induced improvement in pathological changes, serum hormone levels and insulin resistance in rats. In addition, overexpression of SREBP1 repressed insulin-stimulated phosphorylation of insulin receptor β (IR) and AKT in primary granulosa cells. Moreover, upregulation of SREBP1 further exacerbated mitochondrial dysfunction and oxidative stress in granulosa cells isolated from PCOS-like rats. Mechanically, EA treatment suppressed SREBP1 expression through inducing the activation of AMP-activated protein kinase (AMPK) signaling pathway in PCOS-like rats.ConclusionEA intervention alleviated PCOS-like symptoms in rats via improving IR, mitochondrial dysfunction and oxidative stress through regulating SREBP1, a lipid metabolism regulator. Our findings illuminate the novel protective mechanisms of EA in the treatment of PCOS.

Alterations to dual stream connectivity predicts response to aphasia therapy following stroke

BackgroundPredicting aphasia recovery is difficult due to a high variability in treatment response. Detailed measures of treatment response are compounded by a dearth of information that examine brain connections that contribute to clinical improvement. In this study we measure alterations to cortical connectivity pathways during a therapy paradigm to detect whether key brain connections that contribute to language recovery can be detected prior to therapy. MethodsWe conducted a case–control trial with twenty-three adults including eight adults with chronic, post-stroke aphasia. Aphasia patients underwent 12 naming therapy sessions over 4 weeks, consisting of semantic and phonological treatment approaches. High-density electroencephalography (128 channel EEG) was measured prior to therapy and immediately following treatment in patients with aphasia. Analysis via a dynamic causal modelling (DCM) was used to assess which cortical connections significantly correlated with therapy response. ResultsAltered cortical responses in aphasia patients measured bilaterally in a dual stream DCM connectivity model were predictive of treatment-induced improvement in naming. Pre-treatment DCM coupling (i.e., strength of cortical connections) significant correlated with naming improvement for items treated with semantic therapy, as indicated by increased connection strengths between left inferior parietal lobule (LIPL) and inferior frontal gyrus (LIFG, r = .63, pFDR = .016). In particular, the mediating role of contralateral regions significantly influences overall treatment improvement in the latter stages of stroke recovery. ConclusionsOur findings identify a potential means to stratify larger cohorts of patients in neurorehabilitation settings into distinct treatments that are tailored to their individual language deficit.

Phonological cueing of word finding in aphasia: insights from simulations of immediate and treatment effects

ABSTRACT Background: Difficulties with word finding occasionally occur in all speakers and commonly in all aphasia types. An understanding of these difficulties and their treatment-induced improvement is of fundamental scientific and clinical importance. Phonological cueing yields immediate and treatment effects in behavioural and neural measures. Disagreement exists about the locus of the cueing effects in aphasia and whether the effects arise from the same neurocognitive mechanisms as phonological effects in picture naming by healthy speakers. Aims: Computer simulations were conducted to expand our understanding of immediate and treatment effects on word finding in behavioural and neural measures and to examine whether a unified account of the phonological effects in health and disease is possible. Methods & Procedure: Picture naming performance of the WEAVER computer model, which accounts for immediate phonological effects in healthy speakers, was assessed in simulations of immediate and treatment effects of phonological cueing in poststroke aphasia. The model assumes (1) a phonological encoding locus of the cueing effects, (2) a cohort mechanism in cue perception, and (3) activation of lexical and sublexical phonological levels by the cues. Outcomes & Results: The model successfully simulated the empirically observed effects in behavioural naming performance and neural measures. Conclusions: The simulations provide a proof of concept for the idea that immediate and treatment effects of phonological cueing in aphasia arise from the same neurocognitive mechanisms as immediate phonological effects in healthy speakers. This expands our understanding of word finding, associated difficulties, and their improvement by therapy.

Endogenous testosterone determines metformin action on prolactin levels in hyperprolactinaemic men: A pilot study.

Metformin was found to reduce elevated prolactin levels in women but not in men. The current study was aimed at investigating whether endogenous testosterone determines the impact of metformin on lactotroph function in men. This prospective case-control study included 28 men with recently diagnosed type 2 diabetes mellitus and mild or moderate hyperprolactinaemia, 14 of whom had low testosterone levels, while in the remaining 14 ones' testosterone levels were within the reference range. All participants received metformin (2.55-3g daily) for the following 4months. Circulating levels of glucose, insulin, prolactin, testosterone, oestradiol, gonadotropins, sex hormone-binding globulin adrenocorticotropic hormone, insulin-like growth factor-1, thyrotropin and freethyroidhormones were measured at the beginning and at the end of the study. Although metforminreduced plasma glucose levels and improved insulin sensitivity in both groups, this effect was stronger in participants with low testosterone levels. Only in patients with abnormally low testosterone levels, the drug decreased prolactin levels. This effect, which was accompanied by an increase in luteinizing hormone levels, was inversely correlated with baseline testosterone and calculated free testosterone levels, and positively with treatment-induced improvement in insulin sensitivity. In both treatment groups, metformin produced a neutral effect on plasma levels of the remaining hormones. The obtained results suggest that endogenous testosterone may attenuate the impact of metformin on lactotropic cells.

Systolic and diastolic hypertension among patients on hemodialysis: Musings on volume overload, arterial stiffness, and erythropoietin.

Hypertension among patients on hemodialysis is predominantly systolic (either isolated or combined with diastolic hypertension), whereas the scenario of isolated diastolic hypertension is rare and more common in younger patients. Uncontrolled hypertension that persists despite aggressive antihypertensive drug therapy is a reflection of the volume overload that is a prominent mediator of systolic and diastolic BP elevation. Clinical-trial evidence supports the notion that dry-weight probing is an effective strategy to improve BP control, even when overt clinical signs and symptoms of volume overload are not present. Accelerated arterial stiffness influences the patterns and rhythms of interdialytic ambulatory BP and is a major determinant of isolated systolic hypertension in hemodialysis. Posthoc analyses of the Hypertension in Hemodialysis patients treated with Atenolol or Lisinopril (HDPAL) trial, however, suggest that arterial stiffness does not make hypertension more resistant to therapy and is unable to predict the treatment-induced improvement in left ventricular hypertrophy. A combined strategy of sodium restriction, dry-weight adjustment, and antihypertensive medication use was effective in improving ambulatory BP control regardless of the severity of underlying arteriosclerosis in HDPAL. Other nonvolume-dependent mechanisms, such as erythropoietin use, appear to be also important contributors and should be taken into consideration, particularly in younger hemodialysis patients with diastolic hypertension. In this article, we explore the role of volume overload, arterial stiffness, and erythropoietin use as causes of systolic vs diastolic hypertension in patients on hemodialysis. We conclude with clinical practice recommendations and with a call for a "volume-first" approach when managing hemodialysis hypertension.

Metabolomics changes in patients with PAPP-A2 deficiency in response to rhIGF1 treatment

ObjectiveMutations in the pregnancy-associated plasma protein A2 (PAPP-A2) gene have recently been shown to cause postnatal growth failure in two prepubertal patients from a non-consanguineous Spanish family due to the resulting decrease in IGF1 bioavailability. Although a specific pharmacological treatment of this entity is yet to be established, both children received progressive subcutaneous doses (40 to 120 μg/kg) of rhIGF1 twice daily for 2 years. The improvements in growth, hyperinsulinemia and bone mineral density have been previously reported. The objective of this study was to analyze the changes in metabolism associated with these responses to rhIGF1 treatment. DesignHerein we present a detailed characterization of the acute and long-term changes in the metabolic profiles of these two siblings with PAPP-A2 deficiency after the initial injections of rhIGF1 and after two years of treatment. ResultsBy using a GC-MS-based untargeted metabolomics approach, metabolic fingerprinting yielded the identification of 70 serum metabolites including amino acids (46%), organic acids (21%) carbohydrates (16%), fatty acids (14%), and purine bases (3%). Free fatty acids (FFAs) and amino acids showed the largest changes in the compared metabolic profiles, suggesting that rhIGF1 treatment has the greatest effects on lipid and protein metabolic pathways in the PAPP-A2 deficient subjects. ConclusionsThe administration of rhIGF1 resulted in changes related to crucial metabolic pathways, including lipid and protein metabolism, and this could be associated with the previously reported treatment-induced improvement in the mild basal hyperinsulinemia.

Long-term changes in oral health-related quality of life over a period of 5 years in patients treated with narrow diameter implants: A prospective clinical study

ObjectivesThe aim of this study was to assess long-term changes in oral health-related quality of life (OHRQoL) over a period of 5 years in patients treated with narrow diameter implants (NDI) in the mandible for support of an overdenture. MethodsIn this prospective clinical study, a consecutive sample of 20 edentulous patients who had worn sufficient complete dentures for at least 12 weeks was provided with four immediately loaded one-piece titanium NDIs in the mandible. The German 49-item version of the Oral Health Impact Profile (OHIP) was applied to assess OHRQoL at baseline and all follow-ups (4 and 8 weeks, 3, 6, and 12 months, and 3 and 5 years after treatment was finished). ResultsBefore treatment, OHRQoL was substantially impaired indicated by high OHIP summary score (39.9 points). Four weeks after treatment, a substantial treatment-induced drop of OHRQoL impairment was observed (21.8 OHIP points), and at all follow-ups, OHIP scores were lower than at baseline (15.9–26.5 OHIP points; ANOVA: p<.001). Based on mixed-effect linear regression analyses, the treatment-induced effect on OHRQoL improvement over the entire study period was statistically significant for the OHIP summary scores as well as for all four OHIP domains: Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact (all: p<.001). ConclusionsThis study suggests that four immediately loaded NDIs for the support of conventional complete dentures in edentulous patients with substantially impaired OHRQoL may lead to a long-lasting treatment-induced improvement in OHRQoL. Clinical significanceThe provision of four NDI in the edentulous mandible is a promising treatment option for patients with substantial OHRQoL impairment and a positive attitude towards implant treatment. Furthermore, patients can be informed that improvements in OHRQoL are expected to last for at least 5 years.

Perioperative inhibition of β-adrenergic and COX2 signaling in a clinical trial in breast cancer patients improves tumor Ki-67 expression, serum cytokine levels, and PBMCs transcriptome

Catecholamines and prostaglandins are secreted abundantly during the perioperative period in response to stress and surgery, and were shown by translational studies to promote tumor metastasis. Here, in a phase-II biomarker clinical trial in breast cancer patients (n = 38), we tested the combined perioperative use of the β-blocker, propranolol, and the COX2-inhibitor, etodolac, scheduled for 11 consecutive perioperative days, starting 5 days before surgery. Blood samples were taken before treatment (T1), on the mornings before and after surgery (T2&T3), and after treatment cessation (T4). Drugs were well tolerated. Results based on a-priori hypotheses indicated that already before surgery (T2), serum levels of pro-inflammatory IL-6, CRP, and IFNγ, and anti-inflammatory, cortisol and IL-10, increased. At T2 and/or T3, drug treatment reduced serum levels of the above pro-inflammatory cytokines and of TRAIL, as well as activity of multiple inflammation-related transcription factors (including NFκB, STAT3, ISRE), but not serum levels of cortisol, IL-10, IL-18, IL-8, VEGF and TNFα. In the excised tumor, treatment reduced the expression of the proliferation marker Ki-67, and positively affected its transcription factors SP1 and AhR. Exploratory analyses of transcriptome modulation in PBMCs revealed treatment-induced improvement at T2/T3 in several transcription factors that in primary tumors indicate poor prognosis (CUX1, THRa, EVI1, RORa, PBX1, and T3R), angiogenesis (YY1), EMT (GATA1 and deltaEF1/ZEB1), proliferation (GATA2), and glucocorticoids response (GRE), while increasing the activity of the oncogenes c-MYB and N-MYC. Overall, the drug treatment may benefit breast cancer patients through reducing systemic inflammation and pro-metastatic/pro-growth biomarkers in the excised tumor and PBMCs.

INNOVATIVE TREATMENTS FOR TAKAYASU’S ARTERITIS: A FOCUS ON INTERLEUKIN-6 INHIBITORS. THE AUTHORS’ EXPERIENCE WITH TOCILIZUMAB AND A REVIEW OF LITERATURE

The need for further improvement of treatments for Takayasu’s arteritis (TA), the progress in understanding the mechanisms of the disease, and the introduction of biological agents (BA) in rheumatology practice have created preconditions for developing a new TA pharmacotherapy using BA associated with interleukin 6 (IL-6) inhibition. The authors describe their two own cases of tocilizumab (TCZ) use for complicated TA. They analyze the results of TCZ treatment by the data of preliminary trials in 115 patients with TA, which have been published in 30 literature sources, as well as the results of Phase III double-blind, randomized placebo-controlled trials (RPCTs) of the safety and efficacy of TCZ in 18 patients with refractory TA. In one case with a long history of complicated TA, the control of TA activity and the reduction in the dose of glucocorticoids due to TCZ use contributed to the favorable course of pregnancy and labor. In the other case with the onset of TA and focal pulmonary tuberculosis (TB) treated with anti-TB drugs during TCZ monotherapy for 6 months could control TA and achieve TB cure. Preliminary trials showed that TCZ treatment-induced remission or improvement was observed in 85% of patients with TA, including that with a refractory course. RPCTs indicated that the relapse-free survival after 6-month maintenance treatment with TCZ was higher than that in the placebo group (51 and 23%, respectively); but the differences failed to reach statistical significance (p = 0.0596). Due to the fact that a recurrence of TA can occur in patients treated with TCZ, it is appropriate to combine this drug with cytostatic drugs, methotrexate in particular. The use of IL-6 inhibitors should be considered as a potentially effective and relatively safe innovative (off-label) treatment for refractory TA in patients with intolerance or contraindications to standard therapy, which requires further larger randomized clinical trials. Since now there is no universal imaging method that could provide comprehensive information on the status of vessels in TA; the standardization of future clinical trials of BAs requires the improvement of methods for evaluating the efficiency of treatment for TA; moreover, monitoring of disease activity should include a comprehensive assessment of clinical data, current laboratory biomarkers, and instrumental imaging techniques, primarily non-invasive ones.

Nasal obstructive disorders induce medical treatment failure in paediatric persistent allergic rhinitis (The NODPAR Study).

Allergic rhinitis (AR) is the most common chronic disease among children. To characterize the disease, a modified classification of severity (m-ARIA) has recently been validated in AR children. When medical treatment fails, surgery for nasal obstructive disorders (NOD) may be a therapeutic option. Our objective was to assess the prevalence of NOD and their influence in medical treatment response among children with persistent AR (PER). In a prospective, real-life study, 130 paediatric PER patients (13.1±2.8years, females 31.5%, severe rhinitis 49%) referred from Allergy to ENT department were assessed for their response (R, responders; NR, non-responders) to medical treatment (intranasal steroids and antihistamines or antileukotrienes) by direct questioning and nasal symptom visual analogue scale, the presence of NOD (septal deformity, turbinate enlargement and adenoidal hyperplasia), comorbidities, nasal symptoms, rhinitis severity (modified ARIA criterion) and asthma control (International Consensus On Pediatric Asthma criterion). After 2months of treatment, the NR group presented a higher prevalence of obstructive septal deformity and severe inferior turbinate enlargement when compared with the R group. Higher septal deformity and turbinate enlargement scores were strongly associated with treatment refractoriness. The prevalence of severe PER was also higher for the NR group. Higher asthma control scores were associated with the probability of treatment-induced improvement. In paediatric PER patients, medical therapy refractoriness was associated with NOD, mainly septal deformity and turbinate enlargement. In those patients, ENT examination will facilitate an early NOD diagnosis in order to indicate potential corrective surgery.