Evaluating the Potential Impact of Pharmacist Counseling on Medication Adherence Using a Simulation Activity

Objective. To evaluate the impact of counseling in a simulated medication adherence activity.Design. Students were randomized into 2 groups: patient medication monograph only (PMMO) and patient medication monograph with counseling (PMMC). Both groups received a fictitious medication and monograph. Additionally, the PMMC group received brief counseling. A multiple-choice, paper-based survey instrument was used to evaluate simulated food-drug interactions, adherence, and perceptions regarding the activity’s value and impact on understanding adherence challenges.Assessment. Ninety-two students participated (PMMC, n=45; and PMMO, n=47). Overall, a significantly higher incidence of simulated food-drug interactions occurred in the PMMO group (30%) vs the PMMC group (22%) (p=0.02). Doses taken without simulated food-drug interactions were comparable: 46.2% (PMCC) vs 41.9% (PMMO) (p=0.19). The average number of missed doses were 3.2 (PMMC) vs 2.8 (PMMO) (p=0.55). Approximately 70% of the students found the activity to be valuable and 89% believed it helped them better understand adherence challenges.Conclusion. This activity demonstrated the challenges and important role of counseling in medication adherence.     

Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can cause neurological disease in humans, but little is known about the pathogenesis of SARS-CoV-2 infection in the central nervous system (CNS). Herein, using K18-hACE2 mice, we demonstrate that SARS-CoV-2 neuroinvasion and encephalitis is associated with mortality in these mice. Intranasal infection of K18-hACE2 mice with 10⁵ plaque-forming units of SARS-CoV-2 resulted in 100% mortality by day 6 after infection. The highest virus titers in the lungs were observed on day 3 and declined on days 5 and 6 after infection. By contrast, very high levels of infectious virus were uniformly detected in the brains of all the animals on days 5 and 6. Onset of severe disease in infected mice correlated with peak viral levels in the brain. SARS-CoV-2-infected mice exhibited encephalitis hallmarks characterized by production of cytokines and chemokines, leukocyte infiltration, hemorrhage and neuronal cell death. SARS-CoV-2 was also found to productively infect cells within the nasal turbinate, eye and olfactory bulb, suggesting SARS-CoV-2 entry into the brain by this route after intranasal infection. Our data indicate that direct infection of CNS cells together with the induced inflammatory response in the brain resulted in the severe disease observed in SARS-CoV-2-infected K18-hACE2 mice.     

Development of a Cell-Based Luciferase Complementation Assay for Identification of SARS-CoV-2 3CLpro Inhibitors

The 3C-like protease (3CL^pro) of SARS-CoV-2 is considered an excellent target for COVID-19 antiviral drug development because it is essential for viral replication and has a cleavage specificity distinct from human proteases. However, drug development for 3CL^pro has been hindered by a lack of cell-based reporter assays that can be performed in a BSL-2 setting. Current efforts to identify 3CL^pro inhibitors largely rely upon in vitro screening, which fails to account for cell permeability and cytotoxicity of compounds, or assays involving replication-competent virus, which must be performed in a BSL-3 facility. To address these limitations, we have developed a novel cell-based luciferase complementation reporter assay to identify inhibitors of SARS-CoV-2 3CL^pro in a BSL-2 setting. The assay is based on a lentiviral vector that co-expresses 3CL^pro and two luciferase fragments linked together by a 3CL^pro cleavage site. 3CL^pro-mediated cleavage results in a loss of complementation and low luciferase activity, whereas inhibition of 3CL^pro results in 10-fold higher levels of luciferase activity. The luciferase reporter assay can easily distinguish true 3CL^pro inhibition from cytotoxicity, a powerful feature that should reduce false positives during screening. Using the assay, we screened 32 small molecules for activity against SARS-CoV-2 3CL^pro, including HIV protease inhibitors, HCV protease inhibitors, and various other compounds that have been reported to inhibit SARS-CoV-2 3CL^pro. Of these, only five exhibited significant inhibition of 3CL^pro in cells: GC376, boceprevir, Z-FA-FMK, calpain inhibitor XII, and GRL-0496. This assay should greatly facilitate efforts to identify more potent inhibitors of SARS-CoV-2 3CL^pro.     

Occupational concerns associated with regular use of microscope

Objectives

Microscope work can be strenuous both to the visual system and the musculoskeletal system. Lack of awareness or indifference towards health issues may result in microscope users becoming victim to many occupational hazards. Our objective was to understand the occupational problems associated with regular use of microscope, awareness regarding the hazards, attitude and practice of microscope users towards the problems and preventive strategies.

Material and Methods

a questionnaire based survey done on 50 professionals and technicians who used microscope regularly in pathology, microbiology, hematology and cytology laboratories.

Results

Sixty two percent of subjects declared that they were suffering from musculoskeletal problems, most common locations being neck and back. Maximum prevalence of musculoskeletal problems was noted in those using microscope for 11–15 years and for more than 30 h/week. Sixty two percent of subjects were aware of workplace ergonomics. Fifty six percent of microscope users took regular short breaks for stretching exercises and 58% took visual breaks every 15–30 min in between microscope use sessions. As many as 94% subjects reported some form of visual problem. Fourty four percent of microscope users felt stressed with long working hours on microscope.

Conclusions

The most common occupational concerns of microscope users were musculoskeletal problems of neck and back regions, eye fatigue, aggravation of ametropia, headache, stress due to long working hours and anxiety during or after microscope use. There is an immediate need for increasing awareness about the various occupational hazards and their irreversible effects to prevent them.     

Nocturnal variant of benign myoclonic epilepsy of infancy: a case series

Myoclonus is a brief, rapid, involuntary muscle jerk originating in the central nervous system that can be physiological or a symptom of disease. We report a group of five children with excessive myoclonic jerks, only during sleep, and abnormal EEG during the events. Although only one third of the events had EEG epileptiform correlate, the presence of myoclonus without epileptiform EEG correlate has been described in patients with benign myoclonic epilepsy of infancy. We hypothesize that these findings may represent a variant of benign myoclonic epilepsy of infancy.     

CCR9 signaling in dendritic cells drives the differentiation of Foxp3+ Tregs and suppresses the allergic IgE response in the gut

The chemokine receptor CCR9 and its only known ligand CCL25 play an important role in gut inflammation and autoimmune colitis. The function of CCR9-CCL25 in the migration of immune cells is well characterized. However, its role in the immune cell differentiation is mostly not known. Using dextran sodium sulfate (DSS)-induced gut inflammation model, we showed that CCR9⁺ dendritic cells (DCs) specifically CD11b⁻CD103⁺ DCs were significantly increased in the gut-associated lymphoid tissues (GALT) compared to control mice. These CCR9⁺ DCs express lower MHC II and CD86 molecules and had regulatory surface markers (FasL and latency-associated peptide, LAP) in the GALT. In the presence of CCL25, CCR9⁺ DCs promoted in vitro differentiation of Foxp3⁺ regulatory CD4⁺ T cells (Tregs). CCL25-induced differentiation of Tregs was due to intrinsic signaling in the DCs but not through CD4⁺ T cells, which was driven by the production of thymic stromal lymphopoietin (TSLP) and not IL-10. Furthermore, adoptive transfer of CCR9⁺ DCs in C57BL/6 mice promoted Tregs but reduced the Th17 cells in the GALT, and also suppressed the OVA-specific gut-allergic response. Our results suggest CCR9⁺ DCs have a regulatory function and may provide a new cellular therapeutic strategy to control gut inflammation and allergic immune reaction.     

Development of epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): Immunoinformatics approach

Recently, a novel coronavirus (SARS-COV-2) emerged which is responsible for the recent outbreak in Wuhan, China. Genetically, it is closely related to SARS-CoV and MERS-CoV. The situation is getting worse and worse, therefore, there is an urgent need for designing a suitable peptide vaccine component against the SARS-COV-2. Here, we characterized spike glycoprotein to obtain immunogenic epitopes. Next, we chose 13 Major Histocompatibility Complex-(MHC) I and 3 MHC-II epitopes, having antigenic properties. These epitopes are usually linked to specific linkers to build vaccine components and molecularly dock on toll-like receptor-5 to get binding affinity. Therefore, to provide a fast immunogenic profile of these epitopes, we performed immunoinformatics analysis so that the rapid development of the vaccine might bring this disastrous situation to the end earlier.     

Cytological diagnosis of bilateral primary adrenal lymphoma with cutaneous involvement

Primary adrenal lymphoma (PAL) is an extremely rare condition. We describe here, a case of bilateral adrenal lymphoma in a 62‐year‐old man. He later developed subcutaneous masses on the hand and the leg. Fine‐needle aspiration cytology from the adrenals and the soft tissue swellings led to a diagnosis of non‐Hodgkin's lymphoma (NHL). Histopathological examination from the lesion on the leg, confirmed the diagnosis to be B‐cell NHL. The case highlights the cytomorphological findings of this unusual case. Awareness of this entity is essential to differentiate it from other common causes of adrenal enlargement and formulate an appropriate treatment.