Current Evidence, Challenges, and Opportunities of Physiologically Based Pharmacokinetic Models of Atorvastatin for Decision Making

Atorvastatin (ATS) is the gold-standard treatment worldwide for the management of hypercholesterolemia and prevention of cardiovascular diseases associated with dyslipidemia. Physiologically based pharmacokinetic (PBPK) models have been positioned as a valuable tool for the characterization of complex pharmacokinetic (PK) processes and its extrapolation in special sub-groups of the population, leading to regulatory recognition. Several PBPK models of ATS have been published in the recent years, addressing different aspects of the PK properties of ATS. Therefore, the aims of this review are (i) to summarize the physicochemical and pharmacokinetic characteristics involved in the time-course of ATS, and (ii) to evaluate the major highlights and limitations of the PBPK models of ATS published so far. The PBPK models incorporate common elements related to the physicochemical aspects of ATS. However, there are important differences in relation to the analyte evaluated, the type and effect of transporters and metabolic enzymes, and the permeability value used. Additionally, this review identifies major processes (lactonization, P-gp contribution, ATS-Ca solubility, simultaneous management of multiple analytes, and experimental evidence in the target population), which would enhance the PBPK model prediction to serve as a valid tool for ATS dose optimization.

Susceptibility of Alabama argillacea and Chrysodeixis includens (Lepidoptera: Noctuidae) larvae to Beauveria bassiana associated with kaolin

The mortality of the Alabama argillacea and Chrysodeixis includens (Lepidoptera: Noctuidae) larvae caused by the kaolin inert powder and the entomopathogenic fungus Beauveria bassiana were determined under laboratory conditions. Using the caterpillar submersion method, the CG 138 B. bassiana isolate was more pathogenic to A. argillacea than the CG 70, GC 82, ESALQ 634, and ESALQ 645. All five tested isolates caused similar mortality of C. includens. The mortality of first-instar larvae of A. argillacea and C. includens by feeding on leaf-disc impregnated with B. bassiana (CG 138) and kaolin was also determined. Higher A. argillacea mortalities were observed in the B. bassiana (CG 138) treatments, regardless of the presence of kaolin. However, the activity of kaolin + B. bassiana (CG 138) against C. includens was higher than each ingredient alone, indicating an additive action against C. includes larvae. The mortality of A. argillacea and C. includens larvae treated with kaolin + B. bassiana (CG 138) was similar, and the A. argillacea mortality was higher than that of C. includens with kaolin and B. bassiana (GC 138) separated. The treatment kaolin + B. bassiana (CG 138) is promising for the simultaneous management of these two defoliator pests, mainly A. includes. In addition, the monophagous A. argillacea is more susceptible to both kaolin and B. bassiana (GC 138) than the polyphagous C. includens, suggesting that the nutritional ecology plays an important role in the susceptibility of these defoliator species to alternative insecticides.

Panchakarma Therapy for Simultaneous Management of Symptoms due to Multiple Complaints including Hypothyroidism, Leucorrhoea, Cervical Pain - A Case Report

Background: A case report about a female patient has been presented here, who was suffering from multiple complaints including hypothyroidism-(since more than 2 years), leucorrhoea, cervical pain, continuous feverish feeling-(since more than 12 years), etc. According to Ayurvedic texts, the multiple complaints experienced by the patient involve the vitiation of all the three Doshas, i.e. Vata, Pitta and Kapha. Panchakarma Therapy procedures are known to balance the three Doshas, as well as provide tissue nourishing, strengthening and rejuvenating effects.Methodology: Panchakarma therapy was administered for 9 days to the patient. Therapeutic procedures and herbal medicines that pacify the three Doshas, and also provide strengthening, tissue nourishing and rejuvenating effect, were used.Results: The patient experienced notable relief in continuous feverish feeling (90%), neck pain (70%), and white discharge P/V (50%). The complaints of burning mictuition, weakness and fatigue were completely resolved. Overall, the patient was feeling energetic and happy after taking the therapy.Conclusion: Panchakarma therapy showed encouraging results in the simultaneous management of symptoms associated with multiple complaints including hypothyroidism, leucorrhoea, cervical pain, continuous feverish feeling, as well as other associated ailments, in short duration of time.

Left lung and liver hydatid cyst: managed in single surgery

A 35 years male presented with history of pain left chest wall associated with cough, fever and blood in sputum on and off, complaint of pain in abdomen which was dull aching gradually progressive in nature since, 2 months. Radiologically diagnosed to have huge hydatid cysts both in left lung and liver. It is unusual to find such large cysts at multiple sites and organs as in this case. There are reports in the literature of staged management as well as simultaneous management of lung and liver hydatid cysts. Though concomitant cysts in lung and liver may be treated comfortably by one stage surgery. Here both cysts were enucleated in the same sitting by a combined thoracic and abdominal approach (left thoracotomy followed by laparotomy through right subcoastal incision). The technique is safe and results were comparable to two stage surgery. Albendazole treatment in post-operative period helps to prevent recurrence. This report emphasizes that surgical intervention for hydatid cysts at multiple sites done in a single stage is safe, lessens the financial burden and hospital stay by avoiding multiple surgeries and anaesthesia.

Studying Children using Ethnography: Heightened Challenges and Balancing Acts

Scholars have debated how to carry out research with children, particularly about how to generate the most accurate data in an ethically-sensitive fashion. But there has been limited discussion of the practicalities of such research. Relying on our own ethnographic studies with children and families, conducted two decades apart, we argue that studying children heightens routine research challenges and requires the constant balancing of pressures. Our studies highlight difficulties in two broad arenas: the simultaneous management of procedural obligations to children and their gatekeepers (‘the double act’), and the need to juggle satisfying adult norms of interaction while generating and maintaining rapport with children (‘walking the tightrope’). These heightened challenges cannot be solved through use of the “right” method. Rather, they should be acknowledged and met with flexibility, reflexivity, and perseverance. More broadly, open discussion of the difficulties faced while conducting research should not be seen as revealing failings, but as a vital way for scholars to advance the field.