Symptoms as the main problem in primary care: A cross-sectional study of frequency and characteristics

Objective. The aim was to study symptoms managed as the main problem by the general practitioner (GP) and to describe the frequencies and characteristics of presented symptoms when no specific diagnosis could be made. Design. Cross- sectional study. Setting. General practices in the Central Denmark Region. Subjects. In total, 397 GPs included patients with face-to-face contacts during one randomly assigned day in 2008–2009; 7008 patients were included and 5232 presented with a health problem. Main outcome measures. GPs answered a questionnaire after each patient contact. Symptoms and specific diagnoses were subsequently classified using the International Classification of Primary Care (ICPC). Symptom frequency, comorbidity, consultation length, and GP-assessed final outcome and burden of consultations were analysed. Results. The GPs could not establish a specific diagnosis in 36% of patients with health problems. GPs expected that presented symptoms would not result in a future specific diagnosis for half of these patients. Musculoskeletal (lower limb and back) and respiratory (cough) symptoms were most frequent. More GPs had demanding consultations when no specific diagnosis could be made. Higher burden was associated with age, comorbidity, and GP expectancy of persistent symptoms when no diagnosis could be made. Conclusion. Interpretation and management of symptoms is a key task in primary care. As symptoms are highly frequent in general practice, symptoms without a specific diagnosis constitute a challenge to GPs. Nevertheless, symptoms have been given little priority in research. More attention should be directed to evidence-based management of symptoms as a generic phenomenon to ensure improved outcomes in the future.     

Clic1 plays a role in mouse hepatocarcinoma via modulating Annexin A7 and Gelsolin in vitro and in vivo

Clic1 is a member of the family of chloride intracellular ion channels. Previous studies suggest that Clic1 is involved in migration and invasion of the lymphatic metastasis in hepatocarcinoma, however, the mechanism is not fully understood. In the present study, we observed Clic1 is abundant in cytoplasm, higher expression in Hca-F cell than Hca-P cell, and we showed that downregulation of Clic1 by RNA interference was able to markedly enhance the expression of tumor metastasis genes Annexin A7 and Gelsolin in vitro, and downregulation of Annexin A7 and Gelsolin also enhanced the expression of Clic1 in vitro and in vivo. Our results provide novel insight that Clic1 have a role in migration and invasion in hepatocarcinoma maybe via modulating the expression of Annexin A7 and Gelsolin, and provide novel insight into the mechanisms of Clic1 for hepatocarcinoma treatment.     

Serous ovarian tumors: Immunohistochemical profiling as an aid to grading and understanding tumorigenesis

BackgroundThe aim of this study was to evaluate the expression of p53, p16, Wilms tumor gene (WT1), and Mindbomb E3 Ubiquitin Protein Ligase 1 (MIB-1) index by immunohistochemical (IHC) staining in benign, low-grade, and high-grade serous ovarian tumors.MethodsForty-one cases of ovarian serous tumors were included in the study (benign serous tumor [n = 10], low-grade ovarian serous carcinoma [n = 8], and high-grade ovarian serous carcinoma [n = 23]). Expression of p53, p16, WT1, and MIB-1 by IHC was evaluated statistically with the grade of tumor. Semiquantitative scoring system for percentage (0–5) and intensity (1–3) of staining pattern was used to bring about objectivity.Resultsp53, p16, and WT1 showed significantly higher staining scores in ovarian serous carcinoma group than in the benign group (p < 0.05). However, p16 score was not significant in benign versus low-grade tumors. In the carcinoma group, the high-grade serous tumors showed significantly higher staining scores of p53, p16, and WT1 than the low-grade serous tumors (p < 0.05). Papillary serous tumors had comparatively lower p53 and WT1 scores for the same grade of tumor. MIB-1 scores were not significant.Conclusionp53, p16, and WT1 are helpful for the subtyping of serous ovarian tumors as low grade and high grade. WT1 is helpful in establishing primary ovarian serous tumors. The combination of moderate-to-high p53 and WT1 scores provides a robust way of confirming high-grade tumors.     

基于小波能量谱的先天或风湿性心脏病异常心音分类算法研究

目的为解决先天性心脏病或风湿性心脏病异常心音分辨问题,应用离散小波频带能量对异常心音分类算法进行研究。方法采集22人的正常心音和116人的异常心音,对心音信号做离散小波变换,根据病理性心杂音在频域内的分布范围划分5层频带,计算得到各层频带的能量占比,根据单因素方差分析方法,提出了基于小波能量谱的心音分类指标。结果对正常心音和异常心音的4个听诊区域进行了分类,最优分类准确率为92%。区分动脉导管未闭和其余异常心音的最优分类准确率为81.9%。结论基于小波能量谱的心音分类算法无需对心音信号进行分割,提取特征值少,可准确有效地对心音信号进行分类,相较于传统的心音听诊,算法的引入能够在异常心音临床诊断中提供参考数据。     

Type-2 diabetes mellitus-associated cancer risk: In pursuit of understanding the possible link

Background and aimThe insulin resistance-mediated abnormal gluconeogenesis when exceeds a given threshold culminates in type 2 diabetes mellitus (T2DM). This induces severe cellular oxidative stress that may eventually facilitate typical neoplastic transformations. This narrative review aims to portray some of the plausible key mechanistic links bridging T2DM and specific cancers.MethodsA thorough literature search was conducted in the PubMedCentral database to retrieve information from various reputed biomedical reports/articles published from the year 2000. The information regarding the key biochemical signaling pathways mediating the carcinogenic transformation, especially in T2DM patients, was extensively excavated to systematically compile and present a narrative review.ResultsT2DM-associated insulin resistance is known to negatively influence certain crucial genetic and metabolic components (such as insulin/IGFs, PI-3K/Akt, AMPK, and AGEs/RAGE) that may eventually lead to neoplastic transformation. In particular, the risk of developing cancers like pancreatic, colorectal, breast, liver, endometrial, and bladder seems to be more significant in T2DM patients.ConclusionDespite the fact that several studies have suggested a possible correlation between T2DM and cancer mortality, a more detailed research at both pre-clinical and clinical levels is still required so as to fully understand the intricate relationship and make a precise conclusion.     

Diallyl disulfide and diallyl trisulfide in garlic as novel therapeutic agents to overcome drug resistance in breast cancer

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide. It is a cancer that originates from the mammary ducts and involves mutations in multiple genes. Recently, the treatment of breast cancer has become increasingly challenging owing to the increase in tumor heterogeneity and aggressiveness, which gives rise to therapeutic resistance. Epidemiological, population-based, and hospital-based case-control studies have demonstrated an association between high intake of certain Allium vegetables and a reduced risk in the development of breast cancer. Diallyl disulfide (DADS) and diallyl trisulfide (DATS) are the main allyl sulfur compounds present in garlic, and are known to exhibit anticancer activity as they interfere with breast cancer cell proliferation, tumor metastasis, and angiogenesis. The present review highlights multidrug resistance mechanisms and their signaling pathways in breast cancer. This review discusses the potential anticancer activities of DADS and DATS, with emphasis on drug resistance in triple-negative breast cancer (TNBC). Understanding the anticancer activities of DADS and DATS provides insights into their potential in targeting drug resistance mechanisms of TNBC, especially in clinical studies.     

Omarigliptin for the treatment of type 2 diabetes mellitus

Introduction: The estimated global prevalence of diabetes mellitus for adults aged 20-70 in 2015 was 415 million with approximately 90% of diagnosed cases being Type 2 diabetes mellitus (T2DM). Improvements in lifestyle and effective therapies are key to management but due to the progressive nature of T2DM, pharmacotherapy is typically required. Whilst the initial therapy will usually be with metformin, thereafter treatment should be individualised, with consideration of several different second line options. These include the dipeptidyl peptidase-4 (DPP-4) inhibitors, of which omarigliptin is the second once weekly version.

Areas covered: The paper summarises key pharmoacodynamic and pharmacokinetic features and reviews the efficacy and safety trial data of omarigliptin, a once-weekly DPP-4 inhibitor.

Expert opinion: Omarigliptin results in a significant improvement in glycaemia with an effective once weekly pharmacokinetic profile and low risk of drug-drug interactions. It has equivalent efficacy to existing once daily DPP-4 inhibitors and shares a similar side effect profile. It is weight neutral with a significantly lower risk of hypoglycaemia compared with sulphonylureas. Adherence to prescribed medication is poor in patients with T2DM. Once weekly omarigliptin is a welcomed addition to the therapeutic armoury but whether it will improve compliance remains to be seen.