MEMO1 binds iron and modulates iron homeostasis in cancer cells.

Mediator of ERBB2-driven cell motility 1 (MEMO1) is an evolutionary conserved protein implicated in many biological processes; however, its primary molecular function remains unknown. Importantly, MEMO1 is overexpressed in many types of cancer and was shown to modulate breast cancer metastasis through altered cell motility. To better understand the function of MEMO1 in cancer cells, we analyzed genetic interactions of MEMO1 using gene essentiality data from 1028 cancer cell lines and found multiple iron-related genes exhibiting genetic relationships with MEMO1. We experimentally confirmed several interactions between MEMO1 and iron-related proteins in living cells, most notably, transferrin receptor 2 (TFR2), mitoferrin-2 (SLC25A28), and the global iron response regulator IRP1 (ACO1). These interactions indicate that cells with high-MEMO1 expression levels are hypersensitive to the disruptions in iron distribution. Our data also indicate that MEMO1 is involved in ferroptosis and is linked to iron supply to mitochondria. We have found that purified MEMO1 binds iron with high affinity under redox conditions mimicking intracellular environment and solved MEMO1 structures in complex with iron and copper. Our work reveals that the iron coordination mode in MEMO1 is very similar to that of iron-containing extradiol dioxygenases, which also display a similar structural fold. We conclude that MEMO1 is an iron-binding protein that modulates iron homeostasis in cancer cells.

A Rare Case of Acute Cord Compression From Spinal Myeloid Sarcoma: A Complication of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common malignancy in the acute leukemia category. AML is a very aggressive cancer with high mortality. The most common presentations include pancytopenia, bleeding, and recurrent infections. Unlike lymphoma, it rarely presents as a mass. Myeloid sarcoma is a peripheral collection of myeloid cells. Myeloid sarcoma most commonly involves the skin and gingival tissue and rarely it affects the central nervous system. Myeloid sarcoma involving the central nervous system is associated with high mortality. We present a patient with AML which evolved from myelofibrosis presented with acute spinal cord compression and found to have myeloid sarcoma involving the thoracic spinal cord. Despite acute radiation therapy, the patient could not recover her neurological function and passed away shortly after the diagnosis. We discuss the importance of early recognition of the complication due to myeloid sarcoma and treatment with neurosurgical intervention just like other mass causing acute cord compression.

Cross-sectional Study on the Impact of Discount Pricing and Price Competition on Community Pharmacy Practice.

Background Without stipulated legislation, a free pricing policy can lead to a disparity in prices among private healthcare setups. Competition is especially rampant among community pharmacies, especially in the Sabah state of Malaysia, where the recent years have witnessed the steady growth of pharmacy players from Peninsular Malaysia. Thus, this study aimed to examine the impact of price competition and discount pricing on the practice of community pharmacy in Sabah, Malaysia. Methods This was a cross-sectional study using an online questionnaire. Survey participants included community pharmacists practicing in Sabah. The validated and pilot-tested questionnaire consisted of three parts: background information of the pharmacy, attitudes and perception toward medicine prices, and practice of discount pricing. All required data were collected from community pharmacists practicing only in Sabah. Data were then analyzed by using descriptive, Chi-Square, and Kendall's tau-b tests. Results Of the 150 community pharmacists contacted, only 70 responded, providing a response rate of 47%. In terms of pharmacy type, 71% of the respondents were pharmacist-owned independent pharmacies, while 19% were pharmacy chains owned by community pharmacists. The remaining were pharmacies owned by non-pharmacists (10%). Sixty percent of the community pharmacies had been in existence for more than 10 years, with 12% in existence for less than two years, and 28% in existence for three to 10 years. More than 80% of the respondents stated that the business aspect of community pharmacy had overwhelmed the professional practice aspects and that community pharmacists have become providers of products instead of providers of care. In terms of professionalism, 87% also noted that they are being perceived as profiteering in the medicine business at the expense of patients. Conclusions The free market situation in Malaysia for medicine pricing has brought a detrimental consequence for community pharmacists with each one trying to undercut prices. Differing pricing mechanisms of medicines based on the quantity ordered contribute to the problem of discount pricing and price competition. Most community pharmacists, as indicated by this study, want the problem to be addressed.

Pain Intervention for Cancer and Non-cancer Pain: A Retrospective Analysis of Tertiary Care Hospital Experience.

Background With the recent advancement in medicine there has been a great emphasis on the management of chronic pain which remains as one of the major contributing factors for functional limitation in patients as well as a financial burden on healthcare. Newer treatment modalities are aimed at terminating the vicious pain cycles and in this regard peripheral nerve blocks have proven to be very effective. Objectives The aim of this study is to evaluate the effectiveness of interventions for both cancer and non-cancer patients by objective assessment of the patients before and after the procedure. Materials and methods The study included 252 patients who underwent nerve block procedures in Shaukat Khanum Memorial Cancer Hospital from December 2016 to December 2018. The patients were evaluated using numerical rating scale (NRS) for pain, reduction in analgesic doses and patient satisfaction after one and four weeks post procedure. The data was analyzed using mean values and calculating percentages. Results In cancer group, 168 patients were included; mean age 50.49 ± 15.39 with 46.43% females and 53.57% males, the average pain score was 2.62 ± 1.87 post procedure compared with 6.30 ± 1.87 post procedure. 48.21% of the patients reported a reduction in analgesia while 51.79% of the patients kept on using the same analgesics doses. 74.40% of the patients were satisfied and 25.60% patients remained unsatisfied after one week whereas 66.07% were satisfied, 23.81% were not satisfied and 10.12% loss to follow up after four weeks. In non-cancer group 84 patients were included; mean age 56.49 ± 15.79 with 41.67% females and 58.33% males, the average pain score before intervention was 5.99 ± 1.21 and after intervention it was 2.43 ± 1.62. In 73.81% non-cancer patients the analgesics doses were reduced and 70.24% patients were satisfied while 29.76% were unsatisfied after one week. After four weeks 55.95% were satisfied, 22.62% were not satisfied and 21.43% loss to follow up. Conclusion The study showed decrease in pain scores in both group of patients and the importance of nerve blocks as an effective method for chronic pain management. The reduction in the use of other analgesics was also commendable in both the groups.

Ophthalmic Timolol and Hospitalization for Symptomatic Bradycardia and Syncope: A Case Series.

Topical beta-blockers are commonly used for the management of primary open angle glaucoma (POAG). One of the rare but serious side effects of the topical beta-blockers is bradycardia, defined as a heart rate below 60 beats per minute. In few cases, the heart rate drops to much lower level resulting in syncope or symptomatic bradycardia. Topical beta-blockers are still widely used for POAG even though there are much better medications available. We present a series of four cases of symptomatic bradycardia resulting from the use of timolol eye drops and after discontinuation of the eye drops, heart rate improved to normal range (60-100 beats per minute).

Study on the Perception of Staff and Students of a University on Community Pharmacy Practice in Ipoh, Perak, Malaysia.

BACKGROUND: In Malaysia, community pharmacies play an important and vital role in both urban and rural areas with approximately 30% of 12,000 registered pharmacists with annual retention certificate practicing in community pharmacies. The main objective of this study was to find the perception of respondents on the value and necessity of pharmacists. MATERIALS AND METHODS: The questionnaire was divided into two sections: the first section assessed the visits to community pharmacies, purpose, interaction with pharmacy staffs, professional fee, and improvements to pharmacy practices; the second section evaluated the characteristics of respondents including an e-consent form. Data were analyzed using the Statistical Package for the Social Sciences software (version 11.5). RESULTS: The highest number of respondents (66.1%) consulted with the pharmacists for cough and cold, 33.1% for gastric and stomach ailments, and 28.9% for diarrhea and constipation. Only 34% of cases were handled by the pharmacists, whereas 52.1% by the sales assistant. Approximately 88.5% showed satisfaction with the counseling provided. A total of 46.3% did not know whom they dealt with, whereas 51.2% wanted personal attention of the pharmacists instead of the sales assistants. However, 66.9% of respondents preferred to a private consultation room. Records of only 32.2% of respondents were secured by the pharmacies, whereas 42.1% showed interest to pay a professional fee. Moreover, 83.3% agreed the fee of RM5 only, whereas 20.8% agreed to RM10. Among the respondents, majority agreed to pay a fee willingly, but approximately 30% stayed neutral. CONCLUSION: There is a need for the community pharmacists to play vital roles firsthand at the front desk to serve the patients professionally instead of handing over the responsibilities to the sales assistant.

Cross-Sectional Survey of Healthcare Provisions for Female Tuberculosis Patients in Specialized Pulmonary Division from Low Socioeconomic Class in Lahore, Pakistan.

OBJECTIVES: This study aimed to investigate various healthcare provisions for women affected with tuberculosis (TB) from low socioeconomic status and their health seeking behaviors, also whether or not patients feel stigmatized about their disease. INTRODUCTION: Pulmonary tuberculosis has more prevalence in Pakistan as compared to western countries where it occurs predominantly in the immunocompromised individuals and immigrants of certain countries. It is a contagious disease and Pakistan stands at the fifth position with maximum reported cases each year. METHODS: A cross-sectional study was carried at Gulab Devi Hospital, a public sector hospital located in Lahore, through a questionnaire-based survey followed by interviewing all participants. Two hundred seventy-seven female patients, who were already diagnosed with pulmonary tuberculosis, were included in the study. The sample was drawn by non-probability, convenience sampling. Literacy, a major contributor to socioeconomic status, was taken primary criteria to select the sample for the study. RESULTS: The study shows that literacy of patients has no impact on whether they feel stigmatized due to their disease as 42% (45 out of 108) of the literate women felt stigmatized while 39% (65 out of 169) of illiterate women also presented with similar feelings. Furthermore, the research also showed that these patients have no effect on requiring permission for going to the health facility as the study revealed that 62% (67 out of 108) in the literate women required permission while 67% (113 out of 169) illiterate women required permission. CONCLUSION: Pakistani population must be educated about TB and factors associated with the progression and consequences of the disease. It was noted that even educated people feel embarrassed when they develop symptoms of TB, thereby causing the unprecedented delay in effective disease management. To conclude, TB clinic should be opened in each community so that people have easy access to treatment of the disease.

Expression and purification of optimized rolGLP-1, a novel GLP-1 analog, in Escherichia coli BL21(DE3) and its good glucoregulatory effect on type 2 diabetic mice.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that decreases postprandial glycemic excursions by enhancing insulin secretion but with short half-life due to rapid inactivation by enzymatic N-terminal truncation. Therefore, efforts are being made to improve the stability of GLP-1 via modifying its structure or inhibiting dipeptidylpeptidase IV (DPP IV), which is responsible for its degradation. GLP-M, consisting of 10 tandem repeated rolGLP-1 (GLP-1 analog), has been expressed in Pichia pastoris by our laboratory. Although it had a long effect of maintaining glucose homeostasis, redundant amino acids and purification tag limited its application. Here, optimized rolGLP-1(GLPO) with no redundant amino acids and purification tag was constructed by molecular cloning and site-directed mutagenesis, which was expressed efficiently in Escherichia coli BL21(DE3) with the production of 81.5 mg/L, and confirmed by the results of SDS-PAGE electrophoresis and Western Blotting. Then GLP-O was purified via ion exchange chromatography and gel filtration chromatography. The purity of GLP-O was close to 100%. GLP-O could be cut into single rolGLP-1 by trypsin in vitro, and rolGLP-1 had anti-trypsin activity. After oral administration of GLP-O for 4 weeks, the level of blood glucose in type 2 diabetic mice was lowered effectively, and the oral glucose tolerance of mice was improved significantly. These results settled the foundation for further clinical application of GLP-O.