Cardiovascular outcomes trials with incretin-based medications: a critical review of data available on GLP-1 receptor agonists and DPP-4 inhibitors.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors are so called "incretin-based therapies" (IBTs) that represent innovative therapeutic approaches and are commonly used in clinical practice for the treatment of type 2 diabetes mellitus (T2DM). The cardiovascular outcome trials (CVOTs) have provided useful information that has helped to shape changes in clinical practice guidelines for the management of T2DM. At the same time, the mechanisms that may explain the nonglycemic and cardiovascular (CV) benefits of these medications are still being explored. A summary of the main findings from CVOTs performed to-date with particular emphasis on various outcomes and inconsistencies observed in the trials is provided. Overall, available data is favourable to the early deployment of GLP-1RAs in clinical practice, fully in line with recommendations from international scientific guidelines, and based on their effects on glucose metabolism parameters, body weight reduction and CV outcomes. Evidence further suggest that the CV benefits of GLP-1RAs may not be a class effect, with GLP-1 analogues having a greater benefit rather than exendin-based agents.

Understanding the complexities of prevalence of trans fat and its control in food supply in Pakistan.

Pakistan is among the nations with a high intake of trans-fatty acids (TFAs), a major dietary risk factor of noncommunicable diseases (NCDs). Efforts are underway in the country to eliminate industrially produced TFAs from the food supply in keeping with the priority targets of the World Health Organization (WHO) for 2019-2023. We reviewed the TFA content reported in industrially produced foods and discuss the regulatory landscape for TFAs, to facilitate the required policy changes in Pakistan and ultimately eliminate the TFA burden from industrial food products. The study components include review of published research and product labels as well as review of prevailing food regulations for TFA-related information. A set of recommendations was also prepared to eliminate TFAs from Pakistan after national consultation workshops conducted in year 2019. Vanaspati ghee (partially hydrogenated vegetable oil), bakery shortening, hard margarines, and fat spreads are identified as the major sources of TFAs. Federal and provincial food authorities have recently established the limits for TFAs in few products; however, the TFA regulations are insufficient and not in line with global best practices. This study informs a comprehensive national strategy for TFA elimination based on knowledge of TFA prevalence associated regulatory control. We recommend to (1) promote actions toward replacement of traditional vanaspati ghee/bakery fats with healthier alternatives; (2) develop and implement best regulatory practices in line with WHO recommendations; and (3) amend food labeling laws so that clear information will be provided to inform consumers healthy food choices.

Screening, purification and characterization of thermostable, protease resistant Bacteriocin active against methicillin resistant Staphylococcus aureus (MRSA).

BACKGROUND: The emergence of serious issues of multidrug resistance in the past few years have enforced the use of bacteriocins for combating infections. Threat posed to public health by various multidrug resistant (MDR) organisms can be resolved by discovering new antimicrobial proteins with broad spectrum of inhibition. RESULTS: In the current study, Bacteriocin (BAC-IB17) produced by Bacillus subtilis KIBGE-IB17 is found to be effective against different strains of methicillin resistant Staphylococcus aureus (MRSA). The approximate molecular mass of BAC-IB17 is 10.7 kDa. This unique bacteriocin is found to be highly thermostable and pH stable in nature. It also showed its stability against various heavy metals, organic solvents, surfactants and proteolytic enzymes. Amino acid profile of BAC-IB17 clearly showed that this protein mainly consists of non-polar and basic amino acids whereas; some acidic amino acids were also detected. Sequence of first 15 amino acid residues obtained from N-terminal sequencing of BAC-IB17 were NKPEALVDYTGVXNS. CONCLUSIONS: The anti-MRSA property of purified bacteriocin may be used to prevent the spread of MRSA infections. Remarkable features of BAC-IB17 suggests its applications in various pharmaceutical and food industries as it can function under a variety of harsh environmental conditions.

A Rare Case of Spontaneous Pneumocephalus Associated with Nontraumatic Cerebrospinal Fluid Leak.

Introduction. Spontaneous nontraumatic pneumocephalus (PNC) and cerebrospinal fluid (CSF) leaks are both very uncommon conditions. We report a rare case of spontaneous pneumocephalus associated with CSF leak secondary to right sphenoid sinus bony defect without history of trauma. Case Description. 51-year-old Hispanic female with past medical history of hypertension and idiopathic intracranial hypertension (Pseudotumor Cerebri) presented to the emergency room complaining of headache and clear discharge from the right nostril. Physical examination was significant for right frontal sinus tenderness and clear discharge from right nostril. Computed Tomography (CT) scan of the brain showed moderate amount of extra-axial air within the right cerebral hemisphere indicative of pneumocephalus. CT scan of facial bones showed bony defect along the right sphenoid sinus with abnormal CSF collection. The patient was started on intravenous antibiotics for meningitis prophylaxis and subsequently underwent transsphenoidal repair of cerebrospinal fluid leak with abdominal fat graft. CSF rhinorrhea stopped completely after the surgery with near complete resolution of pneumocephalus before discharge. Conclusions. Early identification of pneumocephalus and surgical intervention can help decrease the morbidity and avoid possible complications. Idiopathic intracranial hypertension, although rare, can lead to CSF leak and pneumocepahlus.

Binding effect of proline-rich-proteins (PRPs) on in vitro antimicrobial activity of the flavonoids.

The interaction of the cyanidin, pelargonidin, catechin, myrecetin and kaempferol with casein and gelatin, as proline rich proteins (PRPs), was studied. The binding constants calculated for both flavonoid-casein and flavonoid-gelatin were fairly large (10 (5) -10 (7) M (-1) ) indicating strong interaction. Due to higher proline content in gelatin, the binding constants of flavonoid-gelatin (2.5 × 10 (5) -6.2 × 10 (7) M (-1) ) were found to be higher than flavonoid-casein (1.2 × 10 (5) -5.0 × 10 (7) M (-1) ). All the flavonoids showed significant antibacterial activity against the tested strains. Significant loss in activity was observed due to the complexation with PRPs confirming that binding effectively reduced the concentration of the free flavonoids to be available for antibacterial activity. The decline in activity was corresponding to the values of the binding constants. Though the activities of free catechin and myrecetin were higher compared to pelargonidin, cyanidin and kaempferol yet the decline in activity of catechin and myrecetin due to complexation with casein and gelatin was more pronounced.

Binding effect of proline-rich-proteins (PRPs) on in vitro antimicrobial activity of the flavonoids

The interaction of the cyanidin, pelargonidin, catechin, myrecetin and kaempferol with casein and gelatin, as proline rich proteins (PRPs), was studied. The binding constants calculated for both flavonoid-casein and flavonoid-gelatin were fairly large (105–107 M−1) indicating strong interaction. Due to higher proline content in gelatin, the binding constants of flavonoid-gelatin (2.5 × 105–6.2 × 107 M−1) were found to be higher than flavonoid-casein (1.2 × 105–5.0 × 107 M−1). All the flavonoids showed significant antibacterial activity against the tested strains. Significant loss in activity was observed due to the complexation with PRPs confirming that binding effectively reduced the concentration of the free flavonoids to be available for antibacterial activity. The decline in activity was corresponding to the values of the binding constants. Though the activities of free catechin and myrecetin were higher compared to pelargonidin, cyanidin and kaempferol yet the decline in activity of catechin and myrecetin due to complexation with casein and gelatin was more pronounced.

Her2+ and b-HCG Producing Undifferentiated Gastric Adenocarcinoma.

A 25-year-old Hispanic female with a history of anemia, schizoaffective disorder, and psychosis was admitted for anemia associated with fatigue, weakness, shortness of breath, night sweats, weight loss, and abdominal and lower back pain for the past two months. On routine management, she was found to have a positive serum b-HCG of 80.4 (0-5 mIU/mL) but the patient denied any sexual activity in her life. During her admission, U/S of the pelvis was noncontributory. CT angiogram of the chest was significant for prominent mediastinal and hilar lymph nodes, diffusely thickened stomach suggesting gastric malignancy with multiple hypoenhancing lesions in the liver and diffuse lytic lesions in the spine and sacrum suspicious for metastatic disease. The MRI of the abdomen confirmed the CT angiogram findings. After these findings, EGD was performed which showed lesions in the antrum, body of the stomach, fundus, and cardia on the lesser curvature of the stomach body correlating with carcinoma. The biopsy was positive for Her2, b-HCG producing poorly differentiated gastric adenocarcinoma. Patient underwent one successful round of chemotherapy with Taxotene, Cisplatin, and 5-FU for Stage IV gastric adenocarcinoma.

Separation of polyhydroxyalkanoates-producing bacterial strains using PHA synthase gene and their evaluation for PHA deposition

In this study, a variety of samples were screened for the presence of PHA synthase gene. Results showed that 16 out of 102 isolated were positive for PHA respective genes. The highest prevalence was observed in Pseudomonas aeruginosa. The capability of PHA production was also shown by growing these strains on the defined medium and subsequent analysis using intracellular granules staining and Fourier transform infrared spectroscopy (FT-IR). The microscopic analysis showed that the positive strains accumulated PHA in the cell. The FT-IR analysis showed the presence of PHA peaks in the dried cells as well as in extraction product. P aeruginosa strain P7 showed higher concentration of PHA compared to the others as demonstrated by the highest respective peaks in FT-IR.

Efficacy of non-heme iron fortified diets: a review.

Iron deficiency anemia (IDA) is prevailing around the globe at variable extent. To combat this phenomenon various strategies are popular. One effective strategy is food fortification. A number of reviews are available to discuss the bioavailability of food fortificants exclusively or in special dietary arrangements with specific food vehicles to access their performance in order to overcome the iron deficiency problem. However, little consideration is given to the efficacy studies of these dietary settings. This review is meant for discussing the efficacy of non-heme iron fortified diets.

Study to evaluate the impact of heat treatment on water soluble vitamins in milk.

OBJECTIVES: To evaluate the effect of domestic boiling practice on the contents of water soluble vitamins of loose milk and quantitative comparison of these vitamins in Ultra High Temperature (UHT) treated packaged milk with that of boiled loose milk. METHODS: Loose milk samples were collected from various localities of Karachi city (Pakistan). These samples were boiled in simulated household conditions for 5, 10 and 15 minutes. Ultra High Temperature (UHT) treated packaged milk samples of various brands were obtained from the local market. The aliquots were analyzed for water-soluble vitamins using High Performance Liquid Chromatography (HPLC) technique. The mean values and standard deviations for data were computed and compared as well as level of variations were also determined. RESULTS: Conventional boiling caused destruction of water soluble vitamins in milk i.e. vitamin 81 content in fresh milk decreased from 0.037 mg/100 g to 0.027 mg/100 g after 15 min boiling, whereas vitamin B2 from 0.115 to 0.084 mg/100 g, vitamin B3 0.062 to 0.044 mg/100 g, vitamin B6 0.025 to 0.019 mg/100 g and folic acid 3.38 to 2.40 microg/100 g. This accounted for a post-boiling decrease of about 27, 27, 29, 24 and 36% in vitamins B1, B2, B3, B6 and folic acid respectively. The values for vitamins B1, B2, B3, B6 and folic acid determined in boiled milk were significantly lower than UHT treated packaged milk samples by 25.9, 75.0, 54.5, 63.16 and 38.1% respectively. CONCLUSION: Conventional boiling caused drastic reduction in vitamin levels of loose milk samples. In comparison to this, UHT milk retained high levels of water soluble B-vitamins. Thus it could be envisaged that UHT treated milk provides better water soluble vitamins' nourishment than conventionally boiled milk (JPMA 60:909; 2010).