Identification of potential inhibitors against Corynebacterium diphtheriae MtrA response regulator protein; an in-silico drug discovery approach.

Corynebacterium diphtheriae is a multi-drug resistant bacteria responsible for the life-threatening respiratory illness, diphtheria which can lead to severe Nervous system disorders, mainly infecting the lungs, heart, and kidneys if left untreated. In the current study, Corynebacterium diphtheriae MtrA response regulator protein was targeted, which regulates a two-component system of bacterial pathogenesis, and initiates DNA replication and cell division. In the current study a computational approach have been described for drug development against C. diphtheriae infections by inhibiting MtrA protein by small molecules acting as potential inhibitors against it. Molecular docking analysis of the equilibrated MtrA protein revealed compound-0.2970, compound-0.3029, and compound-0.3016 from Asinex Library as the promising inhibitors based on their lowest binding energies (-9.8 kJ/mol, -9.2 kJ/mol, and -8.9 kJ/mol), highest gold scores (40.53, 47.41, and 48.41), drug-likeness and pharmacokinetic properties. The MD simulation studies of the identified top-ranked inhibitors at 100 ns elucidated the system stability and fluctuations in the binding pocket of MtrA protein. Molecular Dynamics Simulations of the top three docked complexes further revealed that the standard binding pocket was retained ensuring the system stability. The rearrangements of H-bonds, van der Waals, pi-pi, and solid hydrophobic interactions were also observed. The binding free energy calculations (MM/PBSA and MM/GBSA) suggested a fundamental binding capability of the ligand to the target receptor MtrA. Therefore, the current study has provided excellent candidates acting as potent inhibitors for developing therapeutic drugs against C. diphtheriae infections. However, in vivo and in vitro animal experiments and accurate clinical trials are needed to validate the potential inhibitory effect of these compounds.

Understanding the Cardiovascular Fallout of E-cigarettes: A Comprehensive Review of the Literature.

E-cigarettes (ECs) deliver chemicals, including nicotine. They can cause respiratory distress, addiction, cardiovascular effects, and death. More research is needed, especially regarding their impact on the cardiovascular system (CVS) and during pregnancy. Our article aims to fill this gap by summarizing studies elaborating upon the current impact of ECs and the components thereof on the CVS. Acute respiratory distress outbreaks, nicotine addiction, CVS effects, and deaths have been occasionally reported within this cohort, although these events are not uncommon with neighboring age groups. Randomized control trials implying ECs have some contribution toward quitting smoking have been studied. To regulate EC distribution, the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) have created key checkpoints. Additionally, taxation, pricing, age restriction, and media campaigns could be modulated to significantly reduce illicit sales. Education to the users, distributors, and regulators about this product can also play an aiding role in promoting responsible EC use. Another strategy about licensing could be employed, which could incentivize genuine resellers. The effects on CVS and child-bearing by ECs are grim, which calls for strict regulation, awareness, and avoidance by the teetotaler public. They may help individuals stop smoking but not without harming themselves. Strict regulations are necessary to prevent non-judicious use of these devices.

Patterns and Outcomes of dog bite injuries presenting to emergency department in a tertiary care hospital at Karachi.

OBJECTIVES: To assess patterns & outcomes of dog bite injuries coming to a public sector tertiary care hospital in Karachi, Pakistan. METHODS: This was a one-year descriptive cross sectional study from 1st June 2018- 31st May 2019 using consecutive sampling technique. Data of 7512 patients was collected from animal-bite clinic of a tertiary care hospital. Inclusion criteria was animal bite cases that were reported during the dates 1st June 2018 to 31st May 2019, Incomplete records were excluded. Data comprising of time of bite, the location of the victim at the time of bite within the city, animal responsible for the bite, gender and age of victim, date of presentation, site and category of bite (as per WHO criteria) was recorded by the primary investigator. The study was conducted at Jinnah Post-Graduate Medical Centre. RESULTS: Among 7512 participants 85.8% were males, 32.2% victims reported time of bite between morning and noon, 78.8% of bites involved lower limbs. 51.6% of the bites belonged to category 2. Stray dog bites were observed in 90.3% of cases. Outcome showed 54.9% completed their vaccination, while 44.3% did not show for complete follow up, 3.99% bites were grievous & 0.03% reported with developed rabies. CONCLUSION: Research reveals Males belonging to adult age group were most vulnerable, most bites were inflicted in early hours, most common animal inflicting the bites were stray dogs. Many victims did not complete their vaccination from the same centre. Peak of the summer was associated with a decline in number of incidents.

Radiological Mean Age of Fusion of Medial End of the Clavicle: AParameter of Age.

OBJECTIVE: To determine the mean age of fusion of medial end of clavicle by radiography. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Departments of Forensic Medicine, Dow Medical College and Ziauddin University, Karachi, from June 2010 to May 2011. METHODOLOGY: The subjects for this study were selected from various government colleges of Karachi. The subjects were analyzed for age and further confirmation was done by interviews where birth records and other physical parameters of age were also assessed. X-rays chest PA view was taken focusing on the medial end of clavicle; and were examined by a consultant radiologist and complete fusion of the medial end was noted. P-value less than 0.05 was considered significant. RESULTS: The mean age of fusion of medial end of the clavicle was found to be 21 ±1.43 years. Significant difference was observed in male to female age of fusion 21.14 ±1.41 years versus 20.65 ±1.94 years (p > 0.05). Similarly, statistically significant differences were observed between lower to middle income class and higher income class of all society. No difference was observed among various ethnic groups. CONCLUSION: Socio-economic factors, such as diet and nutrition, directly affect bone growth and hence bones' age. The results of fusion of the medial end of the clavicle are not affected by ethnicity; however, it is significantly affected by gender. More studies should be conducted in various parts of the country to make a natural standard in setting up uniform criteria for assessing age at or above 21 years.