Synthesis and biological evaluation of phloroglucinol derivatives possessing α‐glycosidase,acetylcholinesterase, butyrylcholinesterase,carbonic anhydrase inhibitory activity

A series of novel phloroglucinol derivatives were designed, synthesized, characterized spectroscopically and tested for their inhibitory activity against selected metabolic enzymes, including α‐glycosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I and II (hCA I and II). These compounds displayed nanomolar inhibition levels and showed K_i values of 1.14–3.92 nM against AChE, 0.24–1.64 nM against BChE, 6.73–51.10 nM against α‐glycosidase, 1.80–5.10 nM against hCA I, and 1.14–5.45 nM against hCA II.

     

A BAFfling liver aspirate: Metastatic high grade SMARCA4 deficient undifferentiated gastroesophageal junction carcinoma masquerading as a hematolymphoid malignancy

Undifferentiated malignant SMARCA4‐deficient neoplasms are rare, recently characterized, high grade, potentially lethal malignancies. Such tumors are characterized by the loss of BRG1 encoded by SMARCA4, a key component of the Switch/Sucrose Non‐Fermenting (SWI/SNF) chromatin remodeling complex. As this complex, also referred as BAF (BRG1/BRM associated factors) complex, is involved in the epigenetic control of hundreds of genes, including those involved in lineage‐specific differentiation, BAF‐deficient tumors, show minimal or no differentiation and are difficult to classify. Their fine needle aspiration (FNA) cytologic features are still poorly defined. Here, we describe a 70‐year‐old man who presented with thickening of the wall of the distal esophagus and stomach and multiple liver and lung lesions. Liver FNA showed relatively uniform dispersed malignant cells with high nucleus: cytoplasm ratio, scant microvacuolated cytoplasm, eccentric nuclei and prominent nucleoli. Mitoses, necrotic debris, nuclear streak artifact, “ghost cells” and focal rhabdoid cytoplasmic inclusions were also present. The liver core biopsy and GI biopsies demonstrated sinusoidal and respectively submucosal involvement by a high grade undifferentiated malignant neoplasm. The tumor cells were negative for all applied markers on immunohistochemistry and flow cytometry, and only showed CD138 and weak PAX5 staining. After an initial diagnosis of hematolymphoid neoplasm, additional stains showed intact INI1 protein and loss of BRG1 protein immunoexpression, establishing the accurate diagnosis. This case highlights the difficulties and potential pitfalls encountered in the FNA diagnosis of BAF‐deficient tumors, the accurate diagnosis of which is important due to their lack of response to conventional therapy and potential response to targeted therapy.     

How primary care reforms influenced health indicators in Manisa district in Turkey: Lessons for general practitioners

Background: Turkish health reforms began in 2003 and brought some significant changes in primary care services. Few studies in Turkey compare the shift from health centres (HC) to family physicians (FP) approach, which was initiated by reforms.

Objectives: This study compares health status indicators during the HC period before reforms (2003–2007) and the FP period after reforms (2008–2012) in Turkey.

Methods: This study encompasses time series data consisting of the results of a 10-year assessment (2003–2012) in Manisa district. All the data were obtained electronically and by month. The intersection points of the regression curves of these two periods and the beta coefficients were compared using segmented linear regression analysis.

Results: The mean number of follow-up per person/year during the HC period in infants (10.5), pregnant women (6.6) and women (1.8) was significantly higher than the mean number of follow-up during the FP period in infants (6.7), pregnant women (5.6) and women (0.9). Rates of BCG and measles vaccinations were significantly higher during the FP period; however, rates of HBV and DPT were same. The mean number of outpatient services per person/year during the FP period (3.3) was significantly higher than HC period (2.8). Within non-communicable diseases, no difference was detected for hypertension prevalence. Within communicable diseases, there was no difference for rabies suspected bites but acute haemorrhagic gastroenteritis significantly decreased. The infant mortality rate and under five-year child mortality rate significantly increased during the FP period.

Conclusion: Primary care services should be reorganized and integrated with public health services.