Insulin resistance and metabolic syndrome in children of parents with diabetes mellitus

The aim of this prospective study was to research features of insulin resistance and metabolic syndrome in offspring of diabetic parents and to find out whether there is a risk of developing type 2 diabetes mellitus (DM) in these children. Study participants were 30 children of parents with type 1 DM (DM1) (Group I) and 11 children of parents with type 2 DM (DM2) (Group II) who were being followed up in the Diabetes Department of Haseki Research and Training Hospital. The results were compared with a control group of 17 children in the same age group (Group III). There were no statistically significant differences between the Group I and the control group in fasting blood glucose, oral glucose tolerance test values, 1st 2nd and hour insulin, homeostasis model assessment (HOMA) values, body mass index (BMI), systolic and diastolic blood pressure, and lipid parameters, i.e. HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, total cholesterol, and triglycerides. Fasting, 1st and 2nd hour blood insulin levels, HOMA values, BMI, and systolic blood pressure values were significantly higher in Group II compared to the control group (p < 0.05). There were no statistically significant differences between Group II and the control group in lipid parameters, fasting blood glucose, OGTT values, or diastolic blood pressure. We conclude that in our population there is a tendency of insulin resistance and metabolic syndrome in the offspring of parents with DM2, and a risk for developing DM2. Thus, children of patients with DM2 should be followed up so as to recognize early metabolic defects of glucose metabolism and to plan effective preventive efforts to reduce cardiovascular and atherosclerotic risk factors.     

The İmportance of tumor markers in patients undergoing resection for lung metastasis of colorectal carcinoma

Objectives

In patients with suitable conditions, complete resection is a potential curative treatment for lung metastases of colorectal cancers (CRC). Various prognostic factors affecting survival have been reported in these patients. In our study, the prognostic significance of CEA and CA19-9 tumor markers in patients who underwent lung resection for CRC metastasis was researched.

Methods

Fifty-three patients who underwent lung resection for CRC metastasis between January 2015 and July 2021 were included in the study. The relationship between preoperative and postoperative CEA and CA19-9 values, survival times, tumor size, and preoperative CEA and CA19-9 levels were investigated.

Results

Patients with high preoperative and postoperative CEA had shorter survival (OS) compared with patients with lower values (p ≤ 0.001 and p = 0.009, respectively). Disease-free survival (DFS) was also shorter in patients with higher preoperative CEA values (p = 0.008). For patients with higher preoperative and postoperative CA 19–9 values, OS and DFS were shorter (p = 0.013 and p ≤ 0.001) and (p = 0.042 and p ≤ 0.001), respectively. There was a weak positive correlation between preoperative CEA value and tumor size (p = 0.008, Pearson correlation coefficient = 0.360). However, a strong positive correlation between preoperative CA19-9 value and tumor size was discovered (p ≤ 0.001, Pearson correlation coefficient = 0.603).

Conclusion

In our study, it was shown that preoperative-postoperative CEA and CA19-9 levels in patients with metastatic colon carcinoma are associated with overall survival.     

Design,synthesis, molecular docking study,and antibacterial evaluation of some new fluoroquinolone analogues bearing a quinazolinone moiety

BackgroundIncreasing bacterial resistance to quinolones is concerning. Hence, the development of novel quinolones by chemical modifications to overcome quinolone resistance is an attractive perspective in this context.ObjectiveIn this study, it is aimed to design and synthesize a novel series of functionalized fluoroquinolones using ciprofloxacin and sarafloxacin cores by hybridization of quinazolinone derivatives. This objective was tested by a comprehensive set of in vitro antibacterial assays in addition to SAR (structure–activity relationship) characterisation studies.MethodsA nucleophilic reaction of ciprofloxacin and sarafloxacin with 2-(chloromethyl)quinazolin-4(3H)-one in the presence of NaHCO₃ in dimethylformamide (DMF) was performed to obtain the desired compounds 5a-j. Novel compounds were characterised by ¹H, ¹³C- NMR and IR spectroscopy, MS and elemental analysis. In silico pharmacokinetics prediction assays and molecular docking studies were performed to explore the binding characteristics and interactions. Antibacterial activities of the novel compounds were evaluated by Broth microdilution, well diffusion and disc diffusion assays against three gram-positive (Methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus and Enterococcus faecalis) and three gram-negative bacteria (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli).ResultsThe compounds exhibited moderate to good activities against gram-positive bacteria and weak to moderate activities against gram-negative bacteria. Amongst all ciprofloxacin-derivatives, compound 5d was the most potent agent with high antibacterial activity against gram-positive bacteria, including MRSA and S. aureus ((minimum inhibitory concentration (MIC) = 16 nM for both), that is 60 times more potent than ciprofloxacin as parent drug. Compound 5i from sarafloxacin-derivatives was the most potent compound against MRSA and S. aureus (MIC = 0.125 μM). Well diffusion and disk diffusion assay results demonstrated confirmatory outcomes for the quantitative broth microdilution assay. Molecular docking study results were in accordance with the results of antibacterial activity assays.ConclusionThe results of the current study demonstrated that the novel ciprofloxacin and sarafloxacin derivatives synthesized here have promising antibacterial activities. Particularly, compounds 5d and 5i have potential for wider antibacterial applications following further analysis.Graphical abstractElectronic supplementary materialThe online version of this article (10.1007/s40199-020-00373-6) contains supplementary material, which is available to authorized users.     

Perspectives of community pharmacists on conscientious objection to provide pharmacy services: A theory informed qualitative study

BackgroundIn recent years, pharmacists have been opting out of certain pharmacy services, particularly, providing contraceptives, for moral reasons. No research has been conducted on the perceptions of community pharmacists toward conscience objection in a secular state with a mostly Muslim population.ObjectiveThis study aimed to provide an in-depth understanding of the factors related to the beliefs of community pharmacists on conscientious objection to provide pharmacy services contrary to their personal beliefs based on the theory of planned behavior.MethodsSemistructured interviews were conducted with a purposive sampling of community pharmacists. A hybrid deductive and inductive qualitative analysis approach was used on the data that were recorded and transcribed verbatim. Constructs related to attitude, subjective norm, and perceived behavioral control were explored.ResultsIn total, 25 community pharmacists were interviewed. Factors affecting pharmacists’ decision to provide pharmacy services when their personal beliefs included the desire to maintain moral integrity, beliefs about consequences for health care service, profit, patient pressure, precedence of professional values, and care for religious sources.ConclusionMost of the community pharmacists were against the behavior of conscientiously objecting to provide pharmacy services in Turkey because of possible negative consequences on health care. The pharmacists who were willing to act based on their personal beliefs were expecting from various third parties to fulfill certain responsibilities to facilitate to adopt the behavior. This novel study highlights the urgent need for more research and training for community pharmacists serving patients in different socioeconomic contexts in both developed and developing countries.     

Renal Changes and Apoptosis Caused By Subacute Exposure To Aroclor 1254 in Selenium-deficient and Selenium-supplemented Rats

Aroclor 1254 (A1254), a mixture of polychlorinated biphenyls, exerts hepatic, renal, and reproductive toxicity in rodents. This study aimed to determine a protective role of selenium on histopathological changes, oxidative stress, and apoptosis caused by A1254 in rat kidney. It included a control group, which received regular diet containing 0.15 mg/kg Se (C), a Se-supplemented group (SeS) receiving 1 mg/kg Se, a Se-deficient group (SeD) receiving Se-deficient diet of ≤0.05 mg/kg Se, an A1254-treated group (A) receiving 10 mg/kg of Aroclor 1254 and regular diet, an A1254-treated group receiving Se-supplementation (ASeS), and an A1254-treated group receiving Se-deficient diet (ASeD). Treatments lasted 15 days. After 24 h of the last dose of A1254, the animals were decapitated under anaesthesia and their renal antioxidant enzyme activities, lipid peroxidation (LP), glutathione, protein oxidation, and total antioxidant capacity levels measured. Histopathological changes were evaluated by light and electron microscopy. Apoptosis was detected with the TUNEL assay. Kidney weights, CAT activities, and GSH levels decreased significantly in all A1254-treated groups. Renal atrophic changes and higher apoptotic cell counts were observed in the A and ASeD groups. Both groups also showed a significant drop in GPx1 activities (A – 34.92 % and ASeD – 86.46 %) and rise in LP (A – 30.45 % and ASeD – 20.44 %) vs control. In contrast, LP levels and apoptotic cell counts were significantly lower in the ASeS group vs the A group. Histopathological changes and renal apoptosis were particularly visible in the ASeD group. Our findings suggest that selenium supplementation provides partial protection against renal toxicity of Aroclor 1254.     

Fatigue in the mothers of children with cerebral palsy

Purpose: To evaluate fatigue in the mothers of children with cerebral palsy (CP), and to determine its associations with clinical parameters of CP, depression and quality of life (QoL). Method: Ninety children (50 girls and 40 boys) with spastic CP and their mothers were included. Control group comprised mothers of healthy children. Gross motor function classification system (GMFCS) was used for determining functional status. Spasticity was evaluated by using modified Ashworth scale. Fatigue symptom inventory (FSI) was used for assessing maternal fatigue, Nottingham health profile (NHP) for maternal QoL, and Beck Depression Scale (BDS) for maternal depression. Results: Mothers of children with CP scored significantly higher in all FSI subgroups (intensity of fatigue, duration of fatigue and interference with QoL), all NHP subgroups and BDS (p?p?< 0.01). No association was found between FSI and clinical parameters of children with CP including age, gender, type of CP, tonus and functional impairment (p?>?0.05). Conclusions: Our findings indicate that fatigue levels of mothers with CP children are higher than those with healthy children and associated with depression and deterioration in QoL in terms of physical, social and emotional functioning. This should be considered while designing a family centred rehabilitation programme for children with CP.

• Implications for Rehabilitation

• Caring for a child with cerebral palsy has psychological, social and financial impacts on familiesand is associated with increased levels of fatigue among mothers.

• The capacity of current programs and services needs to be strengthened to accommodate theneeds of children with CP and their mothers in order to reduce fatigue of mothers.

• New programs need to be developed to provide psychosocial support for the mothers andto reduce their fatigue as they continue to care for their children.

• Provision of assistive technology devices (particularly suitable wheelchairs) will be useful inreduction of fatigue levels of mothers.

     

Triple‐negative breast cancer—Role of immunology: A systemic review

Recently, the complex role of immune therapy has been the target of increased attention in breast cancer, particularly in triple‐negative breast cancer (TNBC). Although TNBC is sensitive to chemotherapy, the recurrence and mortality rates are worse compared with the other breast cancer types. In addition, TNBC still lacks targeted treatment options. With the improved understanding of the immune system in TNBC, it is expected that new predictive and prognostic markers will be identified, and innovative treatment modalities will be developed. The aim of this review was to provide an overview of the effector cells in the TNBC's microenvironment and to highlight a novel approach to treat this kind of cancer. A computer‐based literature research was carried out using PubMed, American Society of Clinical Oncology Annual Meeting (ASCO) and San Antonio Breast Cancer Symposium (SABCS). To date, studies have shown that tumor‐infiltrating lymphocytes (TILs) and tumor‐associated macrophages ( TAMs) play a very important role in the TNBC's microenvironment. Tumor‐infiltrating lymphocytes can even be considered as biomarkers to predict chemotherapy response in TNBC. Furthermore, TNBC was shown to have immune active subtypes, and therefore, the use of immunotherapy may be an attractive treatment approach. In this respect, several randomized studies have been designed or are currently ongoing to explore the combination of chemotherapy with immunotherapy in TNBC. Combination of chemo‐ and immunotherapy is likely to be beneficial in a subgroup of patients with TNBC.