Impact of Artificial Intelligence on Drug Development and Delivery.

This review explores the transformative impact of AI on drug development and delivery in pharmaceutical sciences, spanning formulation design, real-time monitoring, targeted delivery, and future prospects. The rational design of smart drug carriers, such as AI-optimized liposomes for cancer therapy, optimizes formulations for individual patient needs. AI-driven sensors, exemplified by glucose-monitoring biosensors for diabetics, enable adaptive drug administration, enhancing precision. Despite promises, challenges like biocompatibility, regulations, and ethics persist. Interdisciplinary collaboration and transparent communication are crucial for responsible AI adoption. Anticipated trends include personalized dosage optimization and intelligent nanocarriers. The review underscores AI's potential in reshaping pharmaceuticals for patient-centric care while addressing challenges for widespread adoption.

Comparison of PaO2/FiO2 (PF ratio) to SpO2/FiO2 (SF ratio) and OI to OSI for Predicting Short Term Outcomes in Children with Acute Hypoxemic Respiratory Distress: A Prospective Observational Study.

OBJECTIVES: To compare PaO2/FiO2 (PF ratio) to SpO2/FiO2 (SF ratio) and oxygenation index (OI) to oxygenation saturation index (OSI) for predicting short term outcomes [mortality, progression to ventilation and ventilator free days (VFD)] and compare trends of S/F and OSI in predicting early mortality in children with acute hypoxemic respiratory distress. METHODS: This prospective observational study included 200 consecutive children with acute hypoxemic respiratory distress. Serial PF and SF ratios calculated at 0, 6, 24 and 48 h were compared and their trends were utilized for prediction of 28 d mortality. Same was done in ventilated patients using OI and OSI. RESULTS: SF ratio at admission had a 72% sensitivity and 60% specificity while PF had a sensitivity of 78% and a specificity of 75% for prediction of mortality. The area under the curve (AUC) for SF ratio was 0.82 (CI: 0.688-0.915). Serial SF ratios accurately predicted mortality. OI had sensitivity of 92% and specificity of 95% in predicting 24 and 48 h mortality. OSI had 95% sensitivity and 92% specificity in predicting mortality with AUC 1.000 (CI- 1.00-1.00) at 24 and 48 h post ventilation. Serially increasing OI and OSI trends had an inverse correlation with VFDs (p <0.01). CONCLUSIONS: SF is a reliable surrogate for PF and a useful predictor of progression to ventilation and survival at discharge while OSI is a useful marker of worsening hypoxia and mortality in ventilated patients.

Role of Hematological Parameters in the Early Diagnosis of Neonatal Sepsis.

The major cause of neonatal mortality and morbidity is bacterial sepsis. Blood culture is the most reliable method in neonatal sepsis. This study was conducted to study the usefulness of hematological parameters in the early diagnosis of neonatal sepsis and to assess the most sensitive and specific variables in diagnosing neonatal sepsis. This prospective study was conducted in a tertiary care hospital from January 2017 to January 2018. Peripheral blood smears were prepared from patients with clinical suspicion of sepsis or predisposing perinatal factors for sepsis and stained with Field's stain and examined. The hematological findings were analyzed according to the hematologic scoring system of Rodwell. It was found that immature PMN count, I: M ratio, and I: T ratio had the highest sensitivity (92.06%, 87.30%, and 74.60%, respectively) while I: M ratio, I: T ratio, and degenerative changes in PMN had the highest specificity (97.50%, 96.50%, and 94.0%, respectively) in the prediction of sepsis.

Influence of protein nativity on the stability of bovine serum albumin coated microbubbles.

Protein-coated microbubbles have become one of the emerging platforms in biomedical research as theranostic agents. In recent years, microbubbles have been extensively used as ultrasound contrast agents and carriers of molecular cargoes, pertaining to which several studies have focused on tuning the properties of these bubbles to achieve a higher degree of biocompatibility and extended stability. Synthesis of microbubbles has so far been traditionally carried out with pre-heated proteins like bovine serum albumin (BSA) as shell coatings, owing to the ease in making BSA crosslinked structures through disulfide bridge formation. We, however, have performed experiments to demonstrate that air core microbubbles formed with native BSA are more stable compared with those formed using denatured BSA. The experimental observations have been supported with analytical modeling and computational studies, which offer insights into the effect of BSA conformation in stabilizing the microbubbles shells and prolonging their lifetimes.

Differential in vitro susceptibility to ampicillin/ceftriaxone combination therapy among Enterococcus faecalis infective endocarditis clinical isolates.

OBJECTIVES: To investigate the genomic diversity and ß-lactam susceptibilities of Enterococcus faecalis collected from patients with infective endocarditis (IE). METHODS: We collected 60 contemporary E. faecalis isolates from definite or probable IE cases identified between 2018 and 2021 at the University of Pittsburgh Medical Center. We used whole-genome sequencing to study bacterial genomic diversity and employed antibiotic checkerboard assays and a one-compartment pharmacokinetic-pharmacodynamic (PK/PD) model to investigate bacterial susceptibility to ampicillin and ceftriaxone both alone and in combination. RESULTS: Genetically diverse E. faecalis were collected, however, isolates belonging to two STs, ST6 and ST179, were collected from 21/60 (35%) IE patients. All ST6 isolates encoded a previously described mutation upstream of penicillin-binding protein 4 (pbp4) that is associated with pbp4 overexpression. ST6 isolates had higher ceftriaxone MICs and higher fractional inhibitory concentration index values for ampicillin and ceftriaxone (AC) compared to other isolates, suggesting diminished in vitro AC synergy against this lineage. Introduction of the pbp4 upstream mutation found among ST6 isolates caused increased ceftriaxone resistance in a laboratory E. faecalis isolate. PK/PD testing showed that a representative ST6 isolate exhibited attenuated efficacy of AC combination therapy at humanized antibiotic exposures. CONCLUSIONS: We find evidence for diminished in vitro AC activity among a subset of E. faecalis IE isolates with increased pbp4 expression. These findings suggest that alternate antibiotic combinations against diverse contemporary E. faecalis IE isolates should be evaluated.

Correlation of Robinson's Cytological Grading with Elston and Ellis' Nottingham Modification of Bloom Richardson Score of Histopathology for Breast Carcinoma.

Introduction: Invasive carcinoma of the breast is one of the leading causes of death in women. In developing countries, fine needle aspiration cytology (FNAC) of the breast is used for preoperative diagnosis of breast cancer due to low cost. The grading system of breast carcinoma on FNAC is widely accepted. In the era of neoadjuvant therapy, if grading of breast carcinoma is incorporated in FNAC reports for prognostication, it will be of great help especially in patients with locally advanced disease, older patients with accompanying chronic disease and patients who reject surgery. Hence, there is much to be gained by grading a tumor on FNAC. Materials and methods: The present study was conducted on 40 cases of cytologically diagnosed breast carcinomas. Fine needle aspiration cytology smears were graded by Robinson cytological grading system. All surgical specimens were processed and the histological grading of the resulting slides was done by the Nottingham modification of Bloom Richardson score. Then, the cytological grade was compared with the histological grade and statistical analysis was done. Results:Based on Robinson grading method, cases were classified into grade I (15%), grade II (55%) and grade III (30%). Based on the Nottingham modification of Bloom Richardson (SBR) grading method, the cases were classified as grade I (5%) and grade II and III (47.5%) each. A total concordance rate between both the grading systems was seen in 65% of cases. A positive correlation was found and there was a significant association between Robinson cytological grading and SBR histological grading. Conclusions:Grading breast carcinoma on cytology allows its prognostic evaluation along with diagnostic value without any additional morbidity or expense to the patient. Thus, it is recommended to grade breast carcinomas on FNAC. It helps in deciding the proper line of treatment, so that patients can have a better prognosis.

Ampicillin-Ceftriaxone vs Ampicillin-Gentamicin for Definitive Therapy of Enterococcus faecalis Infective Endocarditis: A Propensity Score-Matched, Retrospective Cohort Analysis.

BACKGROUND: Ampicillin-ceftriaxone (AC) has emerged as an alternative antibiotic regimen for enterococcal infective endocarditis (EIE) with reduced toxicity compared with ampicillin-gentamicin (AG), but evidence regarding its success in reducing EIE-associated death in the United States is limited. METHODS: We conducted a retrospective, propensity score-matched cohort analysis of EIE patients treated with AC or AG between 2010 and 2017 at 3 hospitals in Pittsburgh, Pennsylvania. We assessed all-cause 90-day mortality as the primary outcome and in-hospital mortality, length of hospital stay, hospital readmissions, adverse events, and relapse of bacteremia as the secondary outcomes. RESULTS: A total of 190 patients with EIE (100 treated with AC and 90 with AG) were included. Ninety-day mortality was significantly higher with AC than AG (21% vs 8%; P = .02). After propensity score matching, 56 patients in each group remained for the outcomes analysis. Documented aminoglycoside resistance, presence of annular or aortic abscess, and complete pacemaker removal were the significantly different variables between the 2 matched cohorts. We observed no statistically significant difference in 90-day mortality between the 2 treatment groups (11% vs 7%; P = .55). Adverse events were more common in patients treated with AG (25 vs 39; P = .0091), and more patients in the propensity score-matched AG cohort switched antibiotic regimens than in the AC group (10% vs 49%; P < .0001). CONCLUSIONS: Patients treated with AC demonstrate no significant differences in mortality, treatment failure, or bacteremia relapse compared with AG in a propensity score-matched EIE cohort.

Review: An insight into coronaviruses: Challenges, security and scope.

SARS-CoV2 is a novel coronavirus; the seventh of its species to infect humans. The spread of this virus emerged in Wuhan, China in late December, 2019. Since then, this virus has spread to more than 200 countries and has caused a worldwide pandemic. Being a new species of coronaviruses, any cure or vaccines for this virus has not yet been obtained. A large amount of scientific studies and clinical trials are being carried out across the world to find a potential vaccine for this virus. Current work reports a review of potential drugs and vaccines that may be effective against this virus. Different scientific therapies that may potentially be effective against the SARS-CoV2 virus are also reviewed. The mechanisms of various drugs, their efficiency in various clinical trials and their side effects are also studied.

The Impact of Sensory, Motor and Pain Impairments on Patient- Reported and Performance Based Function in Carpal Tunnel Syndrome.

BACKGROUND: Research has suggested that persistent sensory and motor impairments predominate the symptoms experienced by patients with carpal tunnel syndrome (CTS); with intermittent pain symptoms, being less predominant. OBJECTIVE: The study aims to determine the relative contribution of sensory, motor and pain impairments as contributors to patient-report or performance-based hand function. METHODS: Fifty participants with a diagnosis of CTS confirmed by a hand surgeon and electrodiagnosis were evaluated on a single occasion. Impairments were measured for sensibility, pain and motor performance. A staged regression analysis was performed. In the first step, variables with each of the 3 impairment categories were regressed on the Symptom Severity Scale (SSS) to identify the key variables from this domain. Models were created for both self report (Quick Disabilities of arm, shoulder and hand- Quick DASH) and performance based (Dexterity) functional outcomes. Backward regression modelling was performed for SSS and then, to allow comparability of the importance of different impairments across models, the 7 significant variables from the SSS model were forced into the models. RESULTS: Variables: age, touch threshold and vibration threshold of the little finger of unaffected hand, median-ulnar vibration threshold ratio of affected hand, mean pain tolerance of unaffected hand, grip strength and pinch strength of affected hand, explained 31%, 36% and 63% of the variance in SSS, Quick DASH and dexterity scores, respectively. CONCLUSION: Hand function in patients with CTS is described by variables that reflect sensory status of the median and ulnar nerves, the persons pain threshold, grip and pinch strength impairments and age.

Secoisolariciresinol diglucoside rich extract of L. usitatissimum prevents diabetic colon cancer through inhibition of CDK4.

BACKGROUND: There is increased risk of colon cancer in both men and women having diabetes. The objective of the study was to evaluate the role of Secoisolariciresinol diglucoside rich extract(SRE) of L.usissatisimum(flaxseed) in colon cancer associated with type 2 diabetes mellitus. MATERIAL AND METHODS: Diabetes was induced by administering high fat diet with low dose streptozotocin model. After 6 weeks, diabetes was confirmed and 1,2 dimethylhydrazine(25mg/kg, sc) weekly administration was from 6th to 18th weeks. Rats were treated with the SRE(500mg/kg) orally from 6th to 24th week. After 24 weeks, various biochemical and enzymatic parameters were estimated. Animals were sacrificed and colon tissue was separated and subjected to analysis of histopathological, PCNA studies and mRNA expression of CDK4. RESULTS: Disease control rats depicted hyperglycaemia, hyperinsulinaemia, elevated pro-inflammatory cytokines and cancer biomarker levels, and marked presence of proliferating cells. Treatment with SRE controlled hyperglycaemia, hyperinsulinaemia, reduced pro-inflammatory cytokines and cancer biomarker levels, and decreased no. of proliferating cells. We found that disease control rats depicted over expression of CDK4 mRNA levels which were reduced by SRE treatment. CONCLUSIONS: SRE of L. usitatissimum exhibited chemopreventive effect in colon cancer associated with type 2 diabetes mellitus which might be mediated through inhibition of CDK4.

Impact of an educational intervention on caregivers' beliefs about infant crying and knowledge of shaken baby syndrome.

OBJECTIVE: Shaken baby syndrome (SBS) is the leading cause of traumatic infant death. We examined whether the message about not shaking an infant should be included in the newborn anticipatory guidance provided by pediatric residents. The aim of this study was to determine the impact of an educational intervention (Take 5 Safety Plan for Crying) delivered by pediatric residents at newborn hospital discharge on beliefs about infant crying and knowledge of SBS among caregivers of young infants being treated in an urban primary care center. METHODS: Structured interviews were done in one convenience sample of caregivers before (historical control group) and in a second set of different caregivers after (intervention group) an educational intervention was implemented at hospital discharge. Logistic regression was used to calculate adjusted associations between the intervention and caregivers' beliefs/knowledge. RESULTS: One hundred ten caregivers were in the historical control group and 112 in the intervention group. The intervention group had more mothers and the infants were younger. Controlling for these differences, intervention group caregivers were more likely to state they would take a break if frustrated with infant crying (OR 3.10, 95% CI, 1.62-5.93), were more likely to state frustration caused infant shaking (OR 2.21, 95% CI, 1.20-4.20), and to state their knowledge of SBS was from hospital staff (OR 3.39, 95% CI, 1.61-4.20). CONCLUSION: This targeted postpartum intervention incorporated into newborn anticipatory guidance can influence caregivers' beliefs about infant crying and knowledge of SBS.

Effects of peridialytic oral supplements on nutritional status and quality of life in chronic hemodialysis patients.

OBJECTIVE: Our objective was to determine the effects of peridialytic oral supplements on nutritional markers and quality of life (QOL) in patients receiving maintenance hemodialysis. DESIGN: This trial was open, prospective, nonrandomized, and comparative. SETTING: This study was performed at an outpatient hemodialysis unit in a teaching hospital. PATIENTS: This study included 88 adults with chronic kidney disease at stage 5. INTERVENTION: This study involved directly observed nutrition therapy with >or=1 can of enteral nutrition (Nepro) with each hemodialysis session thrice weekly for 3 months, or standard care. MAIN OUTCOME MEASURE: Changes in biochemical markers of nutritional status and QOL, as measured by the Kidney Disease Quality of Life-Short Form, were determined. RESULTS: Peridialytic oral nutrition resulted in a significant difference between the nutrition and comparison groups in serum albumin change over time (P = .03; repeated-measures analysis of variance with covariates). Mean (+/-SD) serum albumin concentration did not differ between baseline and month 3 in the nutrition group (3.68 +/- 0.33 g/dL vs. 3.75 +/- 0.40 g/dL; P = .12), but in the comparison group, serum albumin levels declined significantly (3.93 +/- 0.34 g/dL at baseline versus 3.81 +/- 0.37 g/dL at month 3; P = .04). The "role-physical" domain score of the Kidney Disease Quality of Life-Short Form significantly changed over time in the nutrition group versus the comparison group (P = .02; repeated-measures analysis of variance with covariates). Nepro was well-tolerated, and greater than 80% of the prescribed therapy was consumed. CONCLUSION: Oral nutrition, as part of structured, directly observed peridialytic therapy in chronic hemodialysis patients, was well-accepted, and resulted in the maintenance of serum albumin levels and QOL with respect to impact of physical health on daily activities. These findings need to be confirmed in a randomized, controlled trial.

Verapamil toxicity resulting from a probable interaction with telithromycin.

OBJECTIVE: To report a case of hypotension and bradyarrhythmia caused by verapamil toxicity in a patient prescribed telithromycin. CASE SUMMARY: A 76-year-old white woman receiving verapamil 180 mg/day for hypertension experienced a sudden onset of shortness of breath and weakness and was found to be profoundly hypotensive and bradycardic, with a systolic blood pressure of 50-60 mm Hg and a heart rate of 30 beats/min. She had been taking telithromycin 800 mg/day for 2 days previously for acute sinusitis. The patient was treated with crystalloids, vasopressors, and transvenous pacing. Approximately 72 hours after admission, her blood pressure and heart rate rapidly returned to normal, and she was discharged several days later. DISCUSSION: Telithromycin is a known substrate of the CYP3A4 system, and several pharmacokinetic interactions can occur by displacement of other drugs from this system. Verapamil is metabolized through several cytochrome P450 isoenzyme systems. Although there are no previous reports of an interaction between these drugs, other possible causes for the patient's symptoms were excluded and the diagnosis of a probable interaction between verapamil and telithromycin leading to verapamil toxicity was made. CONCLUSIONS: Telithromycin is a ketolide antibiotic approved for treatment of respiratory tract infections and acute sinusitis. The potential for clinically significant drug interactions should be considered before using this agent, especially in patients taking other drugs that are metabolized through the CYP3A system. Caution should be exercised when considering the use of this antibiotic in patients receiving verapamil.