Therapeutic strategy of biological macromolecules based natural bioactive compounds of diabetes mellitus and future perspectives: A systematic review.

High blood glucose levels are a hallmark of the metabolic syndrome known as diabetes mellitus. More than 600 million people will have diabetes by 2045 as the global prevalence of the disease continues to rise. Contemporary antidiabetic drugs reduce hyperglycemia and its consequences. However, these drugs come with undesirable side effects, so it's encouraging that research into plant extracts and bioactive substances with antidiabetic characteristics is on the rise. Natural remedies are preferable to conventional anti-diabetic drugs since they are safer for the body, more affordable and have fewer potential adverse effects. Biological macromolecules such as liposomes, niosomes, polymeric nanoparticles, solid lipid nanoparticles, nanoemulsions and metallic nanoparticles are explored in this review. Current drug restrictions have been addressed, and the effectiveness of plant-based antidiabetic therapies has enhanced the merits of these methods. Plant extracts' loading capacity and the carriers' stability are the primary obstacles in developing plant-based nanocarriers. Hydrophilic, hydrophobic, and amphiphilic drugs are covered, and a brief overview of the amphipathic features of liposomes, phospholipids, and lipid nanocarriers is provided. Metallic nanoparticles' benefits and attendant risks are highlighted to emphasize their efficiency in treating hyperglycemia. Researchers interested in the potential of nanoparticles loaded with plant extracts as antidiabetic therapeutics may find the current helpful review.

The impact of diabetes mellitus on the emergence of multi-drug resistant tuberculosis and treatment failure in TB-diabetes comorbid patients: a systematic review and meta-analysis.

Background: The existence of Type 2 Diabetes Mellitus (DM) in tuberculosis (TB) patients is very dangerous for the health of patients. One of the major concerns is the emergence of MDR-TB in such patients. It is suspected that the development of MDR-TB further worsens the treatment outcomes of TB such as treatment failure and thus, causes disease progression. Aim: To investigate the impact of DM on the Emergence of MDR-TB and Treatment Failure in TB-DM comorbid patients. Methodology: The PubMed database was systematically searched until April 03, 2022 (date last searched). Thirty studies met the inclusion criteria and were included in this study after a proper selection process. Results: Tuberculosis-Diabetes Mellitus patients were at higher risk to develop MDR-TB as compared to TB-non-DM patients (HR 0.81, 95% CI: 0.60-0.96, p < 0.001). Heterogeneity observed among included studies was moderate (I2 = 38%). No significant change was observed in the results after sub-group analysis by study design (HR 0.81, 95% CI: 0.61-0.96, p < 0.000). In the case of treatment failure, TB-DM patients were at higher risk to experience treatment failure rates as compared to TB-non-DM patients (HR 0.46, 95% CI: 0.27-0.67, p < 0.001). Conclusion: The results showed that DM had a significant impact on the emergence of MDR-TB in TB-diabetes comorbid patients as compared to TB-non-DM patients. DM enhanced the risk of TB treatment failure rates in TB-diabetes patients as compared to TB-non-DM patients. Our study highlights the need for earlier screening of MDR-TB, thorough MDR-TB monitoring, and designing proper and effective treatment strategies to prevent disease progression.

Current understanding of structural and molecular changes in diabetic cardiomyopathy.

Diabetic Mellitus has been characterized as the most prevalent disease throughout the globe associated with the serious morbidity and mortality of vital organs. Cardiomyopathy is the major leading complication of diabetes and within this, myocardial dysfunction or failure is the leading cause of the emergency hospital admission. The review is aimed to comprehend the perspectives associated with diabetes-induced cardiovascular complications. The data was collected from several electronic databases such as Google Scholar, Science Direct, ACS publication, PubMed, Springer, etc. using the keywords such as diabetes and its associated complication, the prevalence of diabetes, the anatomical and physiological mechanism of diabetes-induced cardiomyopathy, the molecular mechanism of diabetes-induced cardiomyopathy, oxidative stress, and inflammatory stress, etc. The collected scientific data was screened by different experts based on the inclusion and exclusion criteria of the study. This review findings revealed that diabetes is associated with inefficient substrate utilization, inability to increase glucose metabolism and advanced glycation end products within the diabetic heart resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity, and initially subclinical cardiac dysfunction and finally in overt heart failure. Furthermore, several factors such as hypertension, overexpression of renin angiotensin system, hypertrophic obesity, etc. have been seen as majorly associated with cardiomyopathy. The molecular examination showed biochemical disability and generation of the varieties of free radicals and inflammatory cytokines and becomes are the substantial causes of cardiomyopathy. This review provides a better understanding of the involved pathophysiology and offers an open platform for discussing and targeting therapy in alleviating diabetes-induced early heart failure or cardiomyopathy.

Using Culture Sensitivity Reports to Optimize Antimicrobial Therapy: Findings and Implications of Antimicrobial Stewardship Activity in a Hospital in Pakistan.

Background: There are concerns with inappropriate prescribing of antibiotics in hospitals especially broad spectrum in Pakistan and the subsequent impact on antimicrobial resistance rates. One recognized way to reduce inappropriate prescribing is for empiric therapy to be adjusted according to the result of culture sensitivity reports. Objective: Using culture sensitivity reports to optimize antibiotic prescribing in a teaching hospital in Pakistan. Methods: A retrospective observational study was undertaken in Ghurki Trust Teaching Hospital. A total of 465 positive cultures were taken from patients during the study period (May 2018 and December 2018). The results of pathogen identification and susceptibility testing from patient-infected sites were assessed. Additional data was collected from the patient's medical file. This included demographic data, sample type, causative microbe, antimicrobial treatment, and whether empiric or definitive treatment as well as medicine costs. Antimicrobial data was assessed using World Health Organization's Defined Daily Dose methodology. Results: A total of 497 isolates were detected from the 465 patient samples as 32 patients had polymicrobes, which included 309 g-negative rods and 188 g-positive cocci. Out of 497 isolates, the most common Gram-positive pathogen isolated was Staphylococcus aureus (Methicillin-sensitive Staphylococcus aureus) (125) (25.1%) and the most common Gram-negative pathogen was Escherichia coli (140) (28.1%). Most of the gram-negative isolates were found to be resistant to ampicillin and co-amoxiclav. Most of the Acinetobacter baumannii isolates were resistant to carbapenems. Gram-positive bacteria showed the maximum sensitivity to linezolid and vancomycin. The most widely used antibiotics for empiric therapy were cefoperazone plus sulbactam, ceftriaxone, amikacin, vancomycin, and metronidazole whereas high use of linezolid, clindamycin, meropenem, and piperacillin + tazobactam was seen in definitive treatment. Empiric therapy was adjusted in 220 (71.1%) cases of Gram-negative infections and 134 (71.2%) cases of Gram-positive infections. Compared with empiric therapy, there was a 13.8% reduction in the number of antibiotics in definitive treatment. The average cost of antibiotics in definitive treatment was less than seen with empiric treatment (8.2%) and the length of hospitalization also decreased. Conclusions: Culture sensitivity reports helped reduced antibiotic utilization and costs as well as helped select the most appropriate treatment. We also found an urgent need for implementing antimicrobial stewardship programs in hospitals and the development of hospital antibiotic guidelines to reduce unnecessary prescribing of broad-spectrum antibiotics.

Cardiovascular Disease-Related Health Promotion and Prevention Services by Pharmacists in Saudi Arabia: How Well Are They Prepared?

BACKGROUND: Cardiovascular diseases (CVDs) have been identified as the leading reason for morbidity and mortality in Saudi Arabia. Pharmacists play a major role in CVD prevention and health promotion. We aimed to assess the knowledge, attitudes, and involvement of pharmacists in CVD prevention and evaluate the influence of continuing medical education in CVD-prevention services in Saudi Arabia. METHOD: A cross-sectional study was conducted to evaluate the involvement of pharmacists in CVD-related prevention services along with their knowledge and attitudes. A 34-item questionnaire was developed and distributed among the participants. RESULTS: A total of 324 responses were included in the study. More than 60% of pharmacists had provided counseling regarding the importance of healthy lifestyles and self-monitoring CVD risk factors. About half of the participants (49.1%) had never received any CVD-related continuing medical education. Overall, more than 60% of the participants reported positively towards their role in CVD prevention. Lack of time (66%) and lack of educational materials and tools (41%) were the top perceived barriers for providing CVD-prevention and health-promotion activities, followed by lack of skills in using tools (36%) and lack of privacy/space (33%). CONCLUSIONS: The involvement of pharmacists in the prevention of CVD is limited in this study. Further education and capacity building are required to strengthen pharmacists' involvement in CVD-prevention and health-promotion activities.

Impact of Clinical Pharmacist Running Anticoagulation Clinic in Saudi Arabia.

Despite the effectiveness of warfarin in extended anticoagulation, its narrow therapeutic index requires frequent dose adjustments and careful patient monitoring. Thus, we aimed to evaluate the outcomes of clinical pharmacists' intervention in warfarin therapy management in terms of International Normalized Ratio (INR) control, reduction of bleeding, and hospitalization in a tertiary care hospital. An observational retrospective cohort study was conducted on 96 patients taking warfarin therapy in a clinical pharmacist-led anticoagulation clinic. We observed that 39.6% of patients required dose adjustments at their first and second visits. However, dose adjustments during the third, fourth, and fifth weeks were required at 31.1%, 20.8%, and 4.2%, respectively, to achieve INR levels. We also observed that 36.46% of the patients attained the target INR at baseline, which was increased over the first week to the fifth week to 57.29%, 61.46%, 61.46%, 68.75%, and 85.42%, respectively. No one reported the ADR between the third and fifth weeks. Based on our findings, the study strongly suggests that pharmacists' interventions can improve the health-related quality of life of patients undergoing warfarin therapy. Thus, competent pharmacy personnel must be a priority in both usual patient care and critical care among primary care networks.

Expression of Angiopoetin-Like Protein-4 and Kidney Injury Molecule-1 as Preliminary Diagnostic Markers for Diabetes-Related Kidney Disease: A Single Center-Based Cross-Sectional Study.

The purpose of the study was to examine the urinary levels of kidney injury molecule-1 (KIM-1) and angiopoietin-like protein-4 (ANGPTL-4) in individuals with diabetic kidney disease (DKD) and their association with established DKD diagnostic markers such as albuminuria and estimated glomerular filtration rate (eGFR). Levels of ANGPTL-4 and KIM-1 were estimated in urine samples. A total of 135 participants were recruited into three groups: 45 diabetes type 2 patients in the control group and 90 DKD patients in two disease groups. Concentrations of ANGPTL-4 and KIM-1 were conclusively related to the urinary albumin-creatinine ratio (UACR). Also, the levels of both ANGPTL-4 and KIM-1 were negatively associated with the eGFR. Multivariable Poisson regression analysis showed that urinary ANGPTL-4 (PR: 3.40; 95% CI: 2.32 to 4.98; p < 0.001) and KIM-1 (PR: 1.25; 95% CI: 1.14 to 1.38; p < 0.001) were prevalent in DKD patients. Receiver operating characteristic (ROC) analysis of urinary ANGPTL-4 and KIM-1 in the combined form resulted in an area under curve (AUC) of 0.967 (95%CI: 0.932-1.000; p < 0.0001) in the microalbuminuria group and 1 (95%CI: 1.000-1.000; p < 0.0001) in the macroalbuminuria group. The association of urinary levels of ANGPTL-4 and KIM-1 with UACR and eGFR and significant prevalence in the diabetic kidney disease population illustrates the diagnostic potential of these biomarkers.

Antibiotic Utilization Patterns for Different Wound Types among Surgical Patients: Findings and Implications.

Antimicrobial prophylaxis is effective in reducing the rate of surgical site infections (SSIs) post-operatively. However, there are concerns with the extent of prophylaxis post-operatively, especially in low- and middle-income countries (LMICs). This increases antimicrobial resistance (AMR), which is a key issue in Pakistan. Consequently, we conducted an observational cross-sectional study on 583 patients undergoing surgery at a leading teaching hospital in Pakistan with respect to the choice, time and duration of antimicrobials to prevent SSIs. The identified variables included post-operative prophylactic antimicrobials given to all patients for all surgical procedures. In addition, cephalosporins were frequently used for all surgical procedures, and among these, the use of third-generation cephalosporins was common. The duration of post-operative prophylaxis was 3-4 days, appreciably longer than the suggestions of the guidelines, with most patients prescribed antimicrobials until discharge. The inappropriate choice of antimicrobials combined with prolonged post-operative antibiotic administration need to be addressed. This includes appropriate interventions, such as antimicrobial stewardship programs, which have been successful in other LMICs to improve antibiotic utilization associated with SSIs and to reduce AMR.

Integrated Computational Approaches for Inhibiting Sex Hormone-Binding Globulin in Male Infertility by Screening Potent Phytochemicals.

Male infertility is significantly influenced by the plasma-protein sex hormone-binding globulin (SHBG). Male infertility, erectile dysfunction, prostate cancer, and several other male reproductive system diseases are all caused by reduced testosterone bioavailability due to its binding to SHBG. In this study, we have identified 345 phytochemicals from 200 literature reviews that potentially inhibit severe acute respiratory syndrome coronavirus 2. Only a few studies have been done using the SARS-CoV-2 inhibitors to identify the SHBG inhibitor, which is thought to be the main protein responsible for male infertility. In virtual-screening and molecular-docking experiments, cryptomisrine, dorsilurin E, and isoiguesterin were identified as potential SHBG inhibitors with binding affinities of -9.2, -9.0, and -8.8 kcal/mol, respectively. They were also found to have higher binding affinities than the control drug anastrozole (-7.0 kcal/mol). In addition to favorable pharmacological properties, these top three phytochemicals showed no adverse effects in pharmacokinetic evaluations. Several molecular dynamics simulation profiles' root-mean-square deviation, radius of gyration, root-mean-square fluctuation, hydrogen bonds, and solvent-accessible surface area supported the top three protein-ligand complexes' better firmness and stability than the control drug throughout the 100 ns simulation period. These combinatorial drug-design approaches indicate that these three phytochemicals could be developed as potential drugs to treat male infertility.

Preliminary investigation on impact of intergenerational treatment of resveratrol endorses the development of 'super-pups'.

BACKGROUND: Redox biology balances free radical generation and scavenging systems, whereas an imbalanced cellular redox can hasten the onset of various diseases and be regarded as a Pandora's box of ailments. The current study aims to assess the pathophysiological impact of intergenerational resveratrol treatment on diabetes-related cognitive and cardio-renal disorders. MATERIAL AND METHOD: Diabetic rats of the first, second, and third generations were subjected to an intergenerational treatment of resveratrol (20 mg/kg/p.o./day) for 5 months. During this period, the second generation of animals (pups of the first generation) was produced. After the adulthood of second-generation rats, they used to produce third-generation rats. The rats of each generation were evaluated for physiological parameters (BMI, litter size, and life expectancy) and the pathological impact of streptozotocin (55 mg/kg/i.p.), cognitive dysfunctions, and cardio-renal injury. RESULTS: The intergenerational treatment of resveratrol significantly reduced litter size and improved anthropometric parameters, life expectancy, and blood glucose levels in diabetic animals. Resveratrol treatment ameliorates oxidative stress as measured by increased serum nitrite/nitrate concentrations, SOD activity, reduced glutathione concentrations, total serum antioxidant capacity, and diminished serum TBARS level in diabetic animals. Furthermore, diabetic rats receiving intergenerational resveratrol treatment showed improved cognitive behaviour and cardio-renal functionality when compared to the disease control group. CONCLUSION: The intergenerational treatment of resveratrol improved the physiological traits and vital abilities of the heart, kidney, and brain, which endorse its antioxidant potential. Surprisingly, resveratrol treatment increases the second and third generations' resistance to neurobehavioral changes, diabetes, and -associated cardio-renal dysfunction, implying that these generations are "super-pups."

Validation of the General Medication Adherence Scale in Pakistani Patients With Rheumatoid Arthritis.

OBJECTIVE: The aim was to validate the Urdu version of General Medication Adherence Scale (GMAS) in patients with rheumatoid arthritis disease. METHODS: A 2-month (March-April 2019) cross-sectional study was conducted in randomly selected out-patients with rheumatoid arthritis. The sample size was calculated using item-subject ratio of 1:20. The scale was evaluated for factorial, concrete, concurrent, and known group validities. Concrete validity was established by correlating scores of EQ-5D quality of life scale and GMAS adherence score. Concurrent validity was established by correlating the GMAS adherence score with pill count. Analyses for sensitivity were also conducted. Cut-off value was determined through receiver operator curve (ROC), and test-retest method was used to analyze internal consistency and reliability. Data were analyzed through IBM SPSS, IBM AMOS, and MedCalc software. The Urdu version of EQ-5D quality of life questionnaire was used with permission from developers (#ID20884). The study was approved by an ethics committee (#NOV:15). RESULTS: A total of 351 responses were analyzed. The response rate was 98%. Reliability was in acceptable range, i.e., Cronbach α = 0.797. Factorial validity was established by calculation of satisfactory fit indices. Correlation coefficients for concrete and concurrent validities were ρ = 0.687, p < 0.01 and ρ = 0.779, p < 0.01, respectively. Known group validity was established as significant association of adherence score with insurance and illness duration (p < 0.05) that were reported. Sensitivity of the scale was 94%. Most patients had high adherence (N = 159, 45.3%). CONCLUSION: The Urdu version of GMAS demonstrated adequate internal consistency and was validated. These results indicate that it is an appropriate tool to measure medication adherence in Pakistani patients with rheumatoid arthritis.

Cross-culture adaptation and validation of English version of Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS) in patients with rheumatoid arthritis.

AIM: To carry out cross-culture adaptation and validation of the English version of Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS) in patients with rheumatoid arthritis (RA). METHODS: A cross-sectional study was conducted for 2 months in 2 tertiary care hospitals in Karachi, Pakistan. Sample size was calculated based on item-subject ratio. The translation was carried out using standard procedures for translation and cross-culture adaptation. The validation process included estimation of discrimination power, item difficulty index, factorial, convergent, construct and known group validities and reliability. Reliability of the scale was estimated using Kuder-Richardson Formula 20 and a value of σ2  ≥ 0.6 was acceptable. SPSS v23, Remark Classic OMR v6 software and MedCalc Statistical Software v16.4.3, were used to analyze the data. The study was approved by the relevant ethics committee (IRB#NOV:15). RESULTS: The mean score was 7.68 ± 2.52 (95% CI: 7.31-8.05) for 177 patients. The σ2  = 0.601, that is, >0.6, test-retest reliability ρ = .753, P < .05. The average discrimination power = 47.27, average Item Difficulty Index = 0.557. The fit indices were acceptable in a range that established its factorial validity and average factor loading was ≥0.7 which established convergent validity. A significant association (χ2  = 33.074, P < .01) between score interpretation and previous counseling by pharmacists established its construct validity. A significant association (χ2  = 19.113, P < .05) between score interpretation and patient occupation established known group validity. CONCLUSION: The English version of RAKAS was deemed a reliable and validated tool to measure knowledge about disease in Pakistani patients with RA.