Miracle-dz/UniFAR-FTUs huggingface dataset:
Buprenorphine in the treatment of opioid addiction: opportunities, challenges and strategies

Introduction: Buprenorphine follows the success of methadone as another milestone in the history of treatment for opioid addiction. Buprenorphine can be used in an office-based setting where it is clearly effective, highly accepted by patients and has a favorable safety profile and less abuse potential. However, the adoption of buprenorphine treatment has been slow in the USA. Areas covered: This article first reviews the history of medication-assisted opioid addiction treatment and the current epidemic opioid addiction, followed by a review of the efficacy, pharmacology and clinical prescription of buprenorphine in office-based care. We then explore the possible barriers in using buprenorphine and the ways to overcome these barriers, including new formulations, educational programs and policy regulations that strike a balance between accessibility and reducing diversion. Expert opinion: Buprenorphine can align addiction treatment with treatments for other chronic medical illnesses. However, preventing diversion will require graduate and continuing medical education and integrated care models for delivery of buprenorphine to those in need.
Augmentation strategies in partial responder and/or treatment-resistant schizophrenia patients treated with clozapine

Introduction: Although clozapine (CLZ) is considered the best evidence-based therapeutic option for treatment of resistant schizophrenia patients, a significant proportion of CLZ-treated patients show a partial or inadequate response to treatment, leading to increased healthcare cost and poor quality of life for affected individuals. Areas covered: This paper comprises a review of main research in CLZ augmentation strategies for treatment-refractory schizophrenia, with a focus on research conducted between 1990 and 2014. Databases that were searched include: PubMed, CINAHL, EMBASE PsychINFO, AgeLine and Cochrane Database of Systematic Reviews. Primary search terms were ‘clozapine augmentation’, ‘clozapine and add-on’ and ‘treatment-resistant schizophrenia’, with cross reference to specific agents covered in this article. We reviewed the available evidence on CLZ augmentation with antipsychotics, antidepressants, mood stabilizers and other agents. Expert opinion: Many drugs have been evaluated as CLZ add-on therapies without demonstrating convincing efficacy in treating refractory schizophrenia symptoms. More research is needed to better define outcomes in schizophrenia, the topic of treatment-resistance and more well-designed trials are required to establish true efficacy and safety of CLZ augmentation strategies.
Prevalence of incidental maxillary sinus pathologies in dental patients on cone-beam computed tomographic images

Objectives: The aim of the present study was to infer and to record the prevalence of incidental maxillary sinus pathologies in patients presenting with dental problems using the cone-beam computed tomography (CBCT) scans performed for maxillofacial diagnostic purposes. Materials and Methods: This retrospective study has evaluated 201 patients (402 maxillary sinuses consecutive CBCT) for various incidental maxillary sinus pathologies by two observers. Pathologic findings were categorized as mucosal thickening (MT), opacification (OPA), polypoidal-mucosal thickening (PT), others (antrolith and discontinuity of the sinus floor) and no pathologic findings. Correlations for pathologic findings and the factors of age and gender were calculated. Results: The prevalence for total incidental findings is 59.7%. The present study showed MT (35.1%) as most prevalent finding followed by OPA in (16.6%), PT in 7.2% and others in 0.7%. There was no statistically significant difference between gender and between the age groups. There was no statistically significant difference between different indications groups for CBCT scans. Conclusions: The incidental maxillary sinus abnormalities are highly prevalent in the asymptomatic dental patients; hence oral radiologists should be aware of these incidental findings and comprehensively evaluate the entire captured CBCT volume, which can help in early diagnosis, treatment and follow-up of the patient.
The experience of a smoke-free policy in a medium secure hospital

Aims and method A Trust-wide smoke-free policy was introduced in March 2007. This service evaluation retrospectively reviewed the outcome by focusing on recorded changes in behaviour, incidents and prescribing. Results The majority of patients (89%) smoked before the smoke-free policy. There was no significant change in the rate of clinical incidents or the use of tranquillising medication at 3 months and 12 months post-implementation. Clozapine serum levels were raised significantly, necessitating dose reduction in 17% of patients. Fifty-four per cent of patients used nicotine replacement therapy and a small minority continued this treatment for 12 months. Clinical implications Despite initial concerns there were no significant problems in implementation of the smoke-free policy. This was assisted by extensive preparation, education, patient advocacy and access to treatment beforehand.
Clinical evaluation and comparison of the efficacy of coronally advanced flap alone and in combination with platelet rich fibrin membrane in the treatment of Miller Class I and II gingival recessions

Background: The aim of this study was to compare the clinical efficacy of coronally advanced flap (CAF) alone and in combination with autologous platelet rich fibrin membrane (PRF) in Miller′s class I and II gingival recessions. Materials and Method: Thirty isolated Miller class I or II sites in 26 subjects were randomly divided into test (15 sites- CAF+PRF) and control (15 sites- CAF alone). Parameters probing pocket depth (PPD), Recession depth (RD), Clinical attachment loss (CAL), Keratinised tissue width (KTW) and Gingival tissue thickness (GTH) were evaluated at baseline, 3 months and 6 months postoperatively. Data was subjected to statistical analysis. P< 0.05 was considered statistically significant. Results: Mean percentage root coverage was 91.00±19.98% and 86.60±23.83% for test and control group respectively. Difference between the groups in all parameters at baseline, 3 months and 6 months was non significant. Complete root coverage was obtained in 12 (80%) and 11 (73.3%) subjects in test and control group respectively. The difference was found to be non-significant. Both groups showed significant differences in all parameters at 3 and 6 months respectively except difference in gingival tissue thickness which was non-significant in control group at 3 months. Conclusion: Combination of PRF to CAF procedure did not provide any added advantage in term of recession coverage in Miller class I and II recessions. Long term trials with more sample size are needed to validate these findings.
Saroglitazar for the treatment of dyslipidemia in diabetic patients

Introduction: Diabetes and dyslipidemia are commonly associated modifiable risk factors for cardiovascular diseases. Majority of patients with diabetes also suffer from dyslipidemia (diabetic dyslipidemia). Diabetic dyslipidemia is more atherogenic as it is commonly associated with high triglyceride (TG) levels, high proportion of small dense low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol (HDL-C) level (atherogenic dyslipidemia). Currently used pharmacotherapies for the management of diabetes and dyslipidemia like thiazolidinediones (PPAR-γ agonist; for insulin resistance) and fibrates (PPAR-α agonist; for hypertriglyceridemia) have many limitations and side effects. Saroglitazar, a dual PPAR-α/γ agonists, is an emerging therapeutic option with its dual benefit on glycemic and lipid parameters. Areas covered: This paper reviews the clinical development of saroglitazar for the management of diabetic dyslipidemia. The efficacy and safety profile of saroglitazar is reviewed in context to currently available therapy like pioglitazone for diabetes and fibrates for hypertriglyceridemia. In addition, this paper also reviews the association between diabetes and dyslipidemia and the role of TG in reducing cardiovascular events. Expert opinion: Saroglitazar, a dual PPAR-α/γ agonist, is a potential therapeutic option for the management of diabetic dyslipidemia. It has dual benefit of significant improvement in glycemic parameters (glycated hemoglobin and fasting blood glucose) and significant improvement in dyslipidemia (TGs, apolipoprotein B, non-HDL-C). The results of Phase III clinical trials indicate that saroglitazar is devoid of conventional side effects of fibrates and pioglitazone. Future clinical trials of saroglitazar will further establish its place in the management of diabetes, dyslipidemia and associated cardiovascular risk.
The clinical role of serum concentrations of selected cytokines: IL-1β, TNF-α and IL-6 in diagnosis of autoimmune thyroid disease (AITD) in children

Abstract Chronic autoimmune thyroiditis (cAIT) leads to hypothyroidism due to T cell-mediated cytotoxicity in most cases. By contrast, Graves’ disease (GD) with thyrotropin receptor stimulatory autoantibodies cause hyperthyroidism. Cytokines play a crucial role in modulating immune response in both disorders. The aim of study was to evaluate the concentrations of cytokines: IL-1β, TNF-α and IL-6 in these two opposite clinical and hormonal thyroid diseases. The study group consisted of 64 children, 44 newly diagnosed, untreated children with cAIT (n = 22; with hypothyroidism) and GD (n = 22; hyperthyroidism), and the control group of 20 healthy children. Cytokine concentrations were evaluated using the ELISA technique. The studied groups of children did not differ significantly in concentrations of IL-6 (p = 0.48) and TNF-α (p = 0.067). In children with hypothyroidism, we found significantly higher concentrations of IL-1β (median 2.16 pg/ml, IQR 0.87) compared to hyperthyroidism (median 1.39 pg/l, IQR 1.27) (p < 0.01) and the control group (median 1.88 pg/ml, IQR 1.04) (p < 0.05). The results of ROC curve analysis demonstrated the usefulness of IL-1β (AUC = 0.77, p = 0.003) and TNF-α (AUC = 0.691, p = 0.034) as diagnostic parameters in cAIT which enable discrimination of children with autoimmune thyroid disease from healthy individuals. Concentrations of these markers are increased in autoimmune hypothyroidism. We found no significant sex differences in the tested parameters. In conclusion, IL-1β and TNF-α may be considered as markers of hypothyroidism, and could efficiently discriminate between healthy and autoimmune hypothyroid children. Significantly higher concentrations of IL-1β in children with hypothyroidism may be used to distinguish children with cAIT from GD patients.
Odanacatib for the treatment of osteoporosis

Introduction: Osteoporosis and fragility fractures are important public health concerns. Cathepsin K inhibitors, including odanacatib, are a novel class of medications for osteoporosis whose mechanism of action is to directly inhibit bone resorption without killing osteoclasts, thereby permitting the complex coupling between bone resorption and formation to continue. Areas covered: The physiological basis for the mechanism of action of cathepsin K inhibitors is covered in addition to a review of the preclinical, Phase I, Phase II and preliminary Phase III trial data of odanacatib. Expert opinion: Evidence suggests that odanacatib has similar efficacy to bisphosphonates at increasing bone mineral density and decreasing risk of fragility fractures. Although odanacatib may preferentially inhibit bone resorption more than formation, the clinical significance of this difference in mechanism of action is not yet known. A careful analysis of the Phase III trial data is needed with specific attention to adverse events.
Association between functional SIRT1 polymorphisms and the clinical characteristics of patients with autoimmune thyroid disease

Abstract Sirtuin1 (SIRT1) is a Class 3 nicotinamide adenine dinucleotide-dependent histone deacetylase (HDAC) that is thought to be implicated in the protection against autoimmune diseases. However, an association between SIRT1 and autoimmune thyroid disease (AITD) has not been reported. In this study, we selected four single nucleotide polymorphisms (SNPs) in the SIRT1 gene, rs12049646 T/C (termed SNP1), rs12778366 T/C (termed SNP2), rs3758391 T/C (termed SNP3), and rs4746720 T/C (termed SNP4). We genotyped each of these polymorphic sites in 185 patients with Graves’ disease (GD), including 76 patients with intractable GD and 57 patients with GD in remission; 151 patients with Hashimoto’s disease (HD), including 68 patients with severe HD and 54 patients with mild HD; and 96 healthy volunteers. SNP1 and SNP3 were genotyped by the PCR-RFLP method; SNP2 and SNP4 were genotyped using TaqMan® SNP genotyping assays. We also measured the levels of SIRT1 mRNA in CD4+ T cells from 18 control subjects, 16 patients with GD in remission and 14 patients with mild HD using a real-time PCR method. In patients with GD and HD, the C carriers (TC + CC genotypes) of SNP3 showed significantly higher titers of McAb than the TT genotype (p = 0.0261 and p = 0.0309, respectively). Additionally, the T carriers (TT + TC genotypes) of SNP4 showed significantly higher titers of McAb than the CC genotype in patients with GD (p = 0.0079). In conclusion, the polymorphisms in the SIRT1 gene were associated with a greater production of thyroid autoantibodies.
Will personalized drugs for cardiovascular disease become an option? – Defining ‘Evidence-based personalized medicine’ for its implementation and future use

It is generally accepted that the implementation of pharmacogenomics and, more broadly, personalized medicine will have to be ‘evidence-based’. However, there is a lack of consensus on the level of evidence required to justify the use of pharmacogenomic testing in clinical practice. In the cardiovascular field, this lack of agreement has led to somewhat contradicting recommendations by different organizations regarding the clinical utility and use of pharmacogenomic tests or information. Here, we argue that randomized, controlled trials are paramount in order to enable and accelerate the widespread implementation of pharmacogenomics, not only to demonstrate the clinical efficacy and cost-effectiveness of such tests, but because such level of evidence is required to support the considerable changes associated with the implantation of pharmacogenomics in clinical practice.
Pacritinib: a new agent for the management of myelofibrosis?

Introduction: Myelofibrosis (MF) is a clonal haematological disease associated with recurrent somatic gene mutations (JAK2V617F, MPL, CALR) and constitutive activation of the Janus kinase (JAK)/Signal Transducer and Activator of Transcription pathway. MF is often characterised by debilitating symptoms and JAK inhibitors (JAKIs) have revolutionised available therapeutic options. Ruxolitinib, a JAK1 and 2 inhibitor, is the only currently approved agent. Several other JAKIs are undergoing evaluation in the clinical trial setting and Pacritinib, a novel JAK2 and FLT3 inhibitor, is at an advanced stage of investigation with recent completion of a Phase III trial and another ongoing. Areas covered: Within this article we focus on pacritinib, summarising the development, preclinical and up-to-date results from the Phase I – III trials. We present the most recent data on efficacy and safety and indirectly compare this novel JAKI with ruxolitinib. Expert opinion: The kinome array data for pacritinib suggests that it has a range of targets differing to those for ruxolitinib. Pacritinib appears to be an effective agent for the control of MF-related symptoms and splenomegaly with potentially fewer haematological side-effects when compared with ruxolitinib and seems a particularly promising agent for anaemic and thrombocytopenic patients. It is also an attractive drug for potential combination studies due to its good tolerability.
High-risk genotypes HLA-DR3-DQ2/DR3-DQ2 and DR3-DQ2/DR4-DQ8 in co-occurrence of type 1 diabetes and celiac disease

Abstract Shared susceptibility alleles in the HLA region contribute to the co-existence of type 1 diabetes (T1D) and celiac disease (CD). The aim of our study was to identify HLA genotype variations that influence co-occurrence of T1D and CD (T1D + CD) and the order of their onset. Totally 244 patients, 67 with T1D, 68 with CD and 69 with T1D + CD, (split into “T1D first” and “CD first”), were analyzed. Control group consisted of 130 healthy unrelated individuals. Two-tailed Fisher’s exact test was used for statistical analysis. The genetic background of Slovenian CD patients resembled more northern than southern European populations with DR3-DQ2/DR3-DQ2 (odds ratio [OR] = 19.68) conferring the highest risk. The T1D + CD was associated with DR3-DQ2/DR3-DQ2 (OR = 45.53) and even more with DR3-DQ2/DR4-DQ8 (OR = 93.76). DR3-DQ2/DR7-DQ2 played a neutral role in susceptibility for T1D + CD. The order of the onset of T1D or CD in patients with co-occurring diseases was not influenced by HLA risk genotype profile. DR3-DQ2/DR3-DQ2 was associated with an increased risk for developing CD in patients with T1D, whereas patients with CD carrying DR3-DQ2/DR4-DQ8 were at higher risk for developing T1D. In addition to other genetic factors including HLA class I alleles present on DR3-DQ2 extended haplotype, the second extended haplotype may moderate the risk for T1D + CD conferred by DR3-DQ2. Our results suggested that individuals carrying high-risk genotypes DR3-DQ2/DR3-DQ2 or DR3-DQ2/DR4-DQ8 would more likely develop both T1D and CD than either disease alone.
Improved communication between hospital and general practice using online patient discharge summaries

We compared the information contained in traditional ‘To Take Out (TTO)’ discharge prescriptions and dictated letters with the information in discharge summaries from an online system. We also investigated the satisfaction of general practitioners (GPs) with the two types of discharge communication. One group of 30 patients were discharged using traditional TTOs and dictated letters and a second group of 30 patients was discharged using the computer generated summary. The summaries were assessed against the 17 criteria of the Scottish Intercollegiate Guidelines Network. The number of criteria met in the conventional summaries was 10.5 (SD 4.3); the number of criteria met in the computer-generated summaries was 14 (SD 1.2), which was significantly higher (P<0.002). Twelve of the 30 traditional TTOs (40%) were considered illegible. The response rate to the questionnaire was 86%. Eighty-three percent of responding GPs preferred computer generated discharge summaries. The computer generated discharge summaries largely satisfied the guidelines and were enthusiastically received by the GPs surveyed.
Effect of microthreads and platform switching on crestal bone stress levels: a finite element analysis.

BACKGROUND The aims of this study were to investigate the effects of implant microthreads on crestal bone stress compared to a standard smooth implant collar and to analyze how different abutment diameters influenced the crestal bone stress level. METHODS Two-dimensional finite element imaging was used to create a cross-sectional model of an implant (5-mm platform and 13 mm in length) placed in the premolar region of the mandible. The two tapered implant models consisted of one with microthreads at the crestal portion and the other with a smooth neck. The implant model was reverse-engineered to resemble a commercially available microthread implant. Abutments of different diameters (4.0 mm: 20% platform switching; 4.5 mm: 10% platform switching; and 5.0 mm: standard) were loaded with a force of 100 N at 90 degrees vertical and 15 degrees oblique angles. Finite element analysis was used to analyze the stress patterns in bone, especially in the crestal region. RESULTS Upon loading, the microthread implant model had 29% greater stress (31.61 MPa in oblique and 9.31 MPa in vertical) at the crestal bone adjacent to the implant than the smooth-neck implant (24.51 and 7.20 MPa, respectively). When the abutment diameter decreased from 5.0 to 4.5 mm and then to 4.0 mm, the microthread model showed a reduction of stress at the crestal bone level from 6.3% to 5.4% after vertical loading and from 4.2% to 3.3% after oblique loading. The smooth-neck model showed a reduction of stress from 5.6% to 4.9% after vertical loading and from 3.7% to 2.9% after oblique loading. CONCLUSIONS Microthreads increased crestal stress upon loading. Reduced abutment diameter (i.e., platform switching) resulted in less stress translated to the crestal bone in the microthread and smooth-neck groups.
A Prospective Clinical Trial of Arch Width Changes Evaluated through Dental Casts in Consecutively Treated Non-extraction and Extraction Cases

Objective: To compare the dental arch width changes in consecutively treated extraction and non-extraction Class I patients. Materials and methods: Anterior and posterior arch widths of the maxillary and mandibular arches of 21 patients treated by 4 first-premolar extraction and 20 patients treated without extractions were measured on study models using a digital caliper.The initial mean ages were 13.4 ± 1.02 years for the extraction group and 13.1 ± 1.7 years for the non-extraction group. Mean treatment time was 2.7 ± 0.6 years for the extraction group and 2.4 ± 1.0 years for the non-extraction group. The maxillary and mandibular crowding were −5.2 ± 2.8 and −5.9 ± 3.1 mm for the extraction group and −4.1 ± 2.7 and −3.3 ± 2.5 mm for the non-extraction group, respectively. To compare the changes between groups, independent samples t-tests were performed. Results: At the end of treatment, no differences were found between the groups in maxillary intercanine width. The maxillary and mandibular intermolar widths decreased significantly for the extraction group (-0.74mm and -1.59mm, respectively) compared with non-extraction (1.30mm and 0.37mm, respectively). The mandibular intercanine width increased significantly for the extraction group (1.48mm) compared with non-extraction group (0.52mm). Conclusions: Orthodontic treatment with extractions of four first premolarsin Class I patients provided no significant difference in maxillary intercanine width after treatment compared to nonextraction. However, nonextraction treatment produced significantly larger values in maxillary and mandibular intermolar widths than that in the extraction group.
Hyul-Tong-Ryung suppresses PMA-induced MMP-9 expression by inhibiting AP-1-mediated gene expression via ERK1/2 signaling pathway in MCF-7 human breast cancer cells

Our previous study has demonstrated that the methanol extract of Hyul-Tong-Ryung (HM) specifically suppresses the phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-9 (MMP-9) production through the inhibition of MMP-9 mRNA expression in MCF-7 human breast carcinoma cells. However, the molecular mechanisms involved in transcriptional suppression of MMP-9 by HM in PMA-induced MCF-7 cells are not known. In this study, we aimed to elucidate the molecular mechanisms involved in the inhibition of MMP-9 expression by HM in PMA-induced MCF-7 cells. The results of promoter assay and EMSA showed that HM specifically inhibits MMP-9 gene expression by blocking PMA-stimulated activation of activator protein-1 (AP-1). In addition, PMA-stimulated phosphorylation of extracellular signal regulated kinase1/2 (ERK1/2) was suppressed by HM treatment, whereas the phosphorylation of either c-Jun N-terminal kinase (JNK) or p38 mitogen-activated protein kinase (MAPK) was not affected. HM could inhibit the PMA-induced MMP-9 expression through suppression of the transcriptional activity of MMP-9 gene in MCF-7 cells. These results indicate that HM inhibits PMA-induced MMP-9 expression by blocking the activation of activator protein-1 (AP-1) via extracellular signal regulated kinase1/2 (ERK 1/2) signaling pathway.