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Background and Purpose: Specializations within doctor of pharmacy (PharmD) programs allow student pharmacists to advance their knowledge and expertise in a specific area of pharmacy. The purpose of this manuscript is to expand the knowledge of pharmacy specializations within a PharmD program by describing two patient care specializations at a school of pharmacy and their assessment strategies., Educational Activity and Setting: A pediatric pharmacotherapy and acute care pharmacotherapy specialization are described. The development of the specializations and assessment strategies are discussed. Student feedback in addition to postgraduate training and employment in specialization area are used to continually assess the specializations., Findings: Sixty students completed the patient care specializations by completing the specialization coursework, which included extra assignments and a research project. A total of 34 students (57%) who completed the specializations also completed postgraduate year one training., Summary: Patient care specializations allow students to develop skills used in specialty areas, and these added skills may help them be successful in finding postgraduate training related to the specialization. Creating detailed specialization requirements and assessment strategies may ensure that the specialization is of appropriate rigor to enhance specialty-specific skills and knowledge. This report can help other schools of pharmacy with their plans for developing a specialization at their institution., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: There are many challenges associated with longitudinally applying therapeutic knowledge in the pharmacy curriculum. This study investigated student participation using the messaging platform, WhatsApp (Meta Platforms, Inc.), as a discussion-based platform for pharmacy students., Educational Activity and Setting: The created WhatsApp group chat discussion, "The Daily Dose," was a longitudinal learning experience occurring during pharmacy students' last year of clinical rotations or third year of didactic learning. Students were asked daily clinical questions in the application and participation was primarily assessed. This study included a pre-survey, discussion participation assessment, and a post-survey. The surveys assessed student self-evaluations of their learning, clinical confidence levels, board preparedness, and program learning experience feedback., Findings: A total of 115 questions were asked and 37 students voluntarily joined. Students participated by responding to 97% of questions. Of the 37 students who joined, 81% were experiential education students and 19% were didactic education students. A moderator needed to prompt for participation for 34% of the questions. The majority of students (95%) learned something new. Experiential education students were more likely to participate than didactic education students. A moderator may be beneficial to keep the discussion active. Students' self-evaluations of clinical confidence and board preparedness increased after participating in The Daily Dose., Summary: The Daily Dose is an innovative way to engage student discussion and reinforce pharmacy therapeutic knowledge. This tool could be expanded to use with multiple pharmacy learners., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Older people who have been recently discharged from hospital are at increased risk of falls and deterioration in physical functioning., Objective: To investigate the cost-effectiveness of a 12-month home-exercise program for older adults after hospitalization., Method: An economic evaluation was conducted alongside a randomized controlled trial. The analysis was conducted from the health and community service provider perspective. A total of 340 people aged 60 years and older, with a recent hospital admission, were randomized into exercise and usual care control groups. Incremental costs per extra person showing improvement in mobility performance (using the Short Physical Performance Battery), per person indicating improvement in health (self-reported using a 3-point Likert scale) and per quality-adjusted life year (QALY) gained (utility measured using the EQ-5D) were estimated. Uncertainty was represented using cost-effectiveness acceptability curves. Subgroup analyses for participants with better cognition (above the median MMSE score of 28) also were undertaken., Results: The average cost of the intervention was $A751 per participant. The incremental cost-effectiveness of the program relative to usual care was $A22,958 per extra person showing an improvement in mobility, $A19,020 per extra person indicating an improvement in health, and $A77,403 per QALY. The acceptability curve demonstrates that the intervention had an 80% probability of being cost-effective relative to the control at a threshold of $A48,000 per extra person achieving mobility improvement and $A36,000 indicating an improvement in self-reported health. There was no threshold value at which the program can be considered as having an 80% probability of cost-effectiveness for the QALY outcome. Subgroup analyses for participants with better cognitive status indicated improved cost-effectiveness for all outcomes., Conclusion: The exercise intervention appeared to offer reasonable value for money for mobility outcomes and self-reported health status. Value for money for all measures was greater in the higher cognitive status subgroup., (Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting., Methods: We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10(-6)) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults., Results: rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10(-10)) and replication cohorts (p = 5.65 × 10(-8)). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10(-8), and rs6813517 [SPOCK3], p = 2.58 × 10(-8)) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism., Conclusions: This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Posttraumatic stress disorder (PTSD) results from the formation of a strong memory for the sensory-perceptual and affective representations of traumatic experiences, which is detached from the corresponding autobiographical context information. Because WWC1, the gene encoding protein KIBRA, is associated with long-term memory performance, we hypothesized that common WWC1 alleles influence the risk for a lifetime diagnosis of PTSD., Methods: Traumatic load and diagnosis of current and lifetime PTSD were assessed in two independent African samples of survivors from conflict zones who had faced severe trauma (n = 392, Rwanda, and n = 399, Northern Uganda, respectively). Array-based single nucleotide polymorphism (SNP) genotyping was performed. The influence of WWC1 tagging SNPs and traumatic load on lifetime PTSD was estimated by means of logistic regression models with correction for multiple comparisons in the Rwandan sample. Replication analysis was performed in the independent Ugandan sample., Results: An association of two neighboring SNPs in almost complete linkage disequilibrium, rs10038727 and rs4576167, with lifetime PTSD was discovered in the Rwandan sample. Although each traumatic event added to the probability of lifetime PTSD in a dose-dependent manner in both genotype groups, carriers of the minor allele of both SNPs displayed a diminished risk (p = .007, odds ratio = .29 [95% confidence interval = .15-.54]). This effect was confirmed in the independent Ugandan sample., Conclusions: This study reveals an association between two WWC1 SNPs and the likelihood of PTSD development, indicating that this memory-related gene might be involved in processes that occur in response to traumatic stress and influence the strengthening of fear memories., (Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

A novel murine system was developed to study the in vivo localization of xenotransplanted human cells and assess their therapeutic effect in an authentic model of disease. The beta-glucuronidase (GUSB) mutation of the mucopolysaccharidosis type VII (MPSVII) mouse was backcrossed onto the nonobese diabetic/severe combined immunodeficient (NOD/SCID) xenotransplantation strain. The resulting NOD/SCID/MPSVII mice displayed the characteristic features of lysosomal storage disease because of GUSB deficiency and were also capable of engrafting human cells. Human CD34+ hematopoietic progenitor cells from healthy, GUSB+ donors engrafted NOD/SCID/MPSVII mice in a manner similar to that of standard NOD/SCID mice. Six to 12 weeks following transplantation, 1% to 86% of the host bone marrow was positive for human CD45. By using a GUSB-specific histochemical assay, human engraftment was detected with single-cell sensitivity not only in well-characterized hematopoietic tissues like bone marrow, spleen, lymph node, and thymus, but also in other nonhematopoietic organs like liver, kidney, lung, heart, brain, and eye. Quantitative measurements of GUSB activity confirmed this expansive tissue distribution. The GUSB-specific assays were validated for their accuracy in identifying human cells through colocalization of human CD45 expression with GUSB activity in tissues of mice receiving transplants. An analysis of the therapeutic effects of engrafted human cells revealed a reduction of pathologic storage material in host organs, including the bone, spleen, and liver. Such xenotransplantation experiments in the NOD/SCID/MPSVII mouse represent a powerful approach to both study the in vivo biology of human cells and gather preclinical data regarding treatment approaches for a human disease.

The toxicity of preparative regimens render neonatal bone marrow transplantation (BMT) for progressive childhood diseases a controversial treatment. Ablative BMT in neonatal mice with or without the lysosomal storage disease mucopolysaccharidosis type VII (MPS VII) show high morbidity and developmental disruption of both brain and bone structure. In this investigation, BMT was performed with a high dose of congenic, normal bone marrow into nonablated newborn mice. Recipients had lifelong, multilineage, peripheral blood chimerism with the donor beta-glucuronidase-positive (GUS(+)) cells that was both well tolerated and therapeutic. Three daily injections of normal adult marrow increased the average life span by at least 6 months and corrected the functional breeding deficits typical of the MPS VII mice. Twelve months after injection, several structural features of femurs were more like that of normal mice than of untreated MPS VII mice. Periosteal circumference and bone cortical thickness were significantly improved in males and cortical density did not differ significantly from values in normal females. Significant reduction of lysosomal glycosaminoglycan storage corresponded directly with GUS enzyme activity and percentage of histochemically GUS(+) cells in visceral organs and hematopoietic tissues such as thymus, spleen, peripheral blood, and bone marrow. By all criteria tested, BMT into neonatal MPS VII mice in the absence of any preparative regimen is a successful therapy.

Bone marrow transplantation (BMT) is relatively effective for the treatment of lysosomal storage diseases. To better understand the contribution of specific hematopoietic lineages to the efficacy of BMT, we transplanted beta-glucuronidase-positive mononuclear phagocytes derived from either the peritoneum or from bone marrow in vitro into syngeneic recipients with mucopolysaccharidosis type VII (MPS VII). Cell surface marking studies indicate that the bone marrow-derived cells are less mature than the peritoneal macrophages. However, both cell types retain the ability to home to tissues rich in cells of the reticuloendothelial system after intravenous injection into MPS VII mice. The half-life of both types of donor macrophages is approximately 7 days, and some cells persist for at least 30 days. In several tissues, therapeutic levels of beta-glucuronidase are present, and histopathologic analysis demonstrates that lysosomal storage is dramatically reduced in the liver and spleen. Macrophages intravenously injected into newborn MPS VII mice localize to the same tissues as adult mice but are also observed in the meninges and parenchyma of the brain. These data suggest that macrophages play a significant role in the therapeutic efficacy of BMT for lysosomal storage diseases and may have implications for treatments such as gene therapy.

MPS VII mice are deficient in beta-glucuronidase and share many clinical, biochemical, and pathologic characteristics with human mucopolysaccharidosis type VII (MPS VII). We have shown that syngeneic bone marrow transplantation (BMT) prolongs survival and reduces lysosomal storage in many organs of the MPS VII mouse. In this report, we quantify the hearing loss and determine the impact of syngeneic BMT on the development of deafness and the associated pathology in the MPS VII mouse. Eleven weeks after syngeneic BMT performed at birth, treated MPS VII mice had normal auditory-evoked brainstem responses (ABR), whereas untreated MPS VII mice had ABR thresholds 43 dB higher than normal. Treated MPS VII mice had beta-glucuronidase-positive cells in the temporal bone and in the subepithelial connective tissue of the external auditory canal. There was less thickening of the tympanic membrane and middle ear mucosa and decreased distortion of the ossicles and the cochlear bone. Although transplanted MPS VII mice had increased ABR thresholds by 33 weeks of age, four of the six had thresholds 12 to 32 dB lower than untreated mutants. These data indicate that syngeneic BMT in newborn MPS VII mice prevents early hearing loss and, in some animals, results in long-term improved auditory function.

The gusmps/gusmps mouse has no beta-glucuronidase activity and develops murine mucopolysaccharidosis type VII (MPS VII). The clinical and pathologic abnormalities are similar to those found in humans with severe MPS VII. Mutant mice are dysmorphic, dwarfed, and have a shortened life span. Pathologic findings include widespread lysosomal storage. To determine whether bone marrow transplantation (BMT) corrects these abnormalities, genetically identical mutant animals were given syngeneic bone marrow transplants using cells from +/+ mice. Initial experiments showed that levels of beta-glucuronidase activity in recipient tissues correlated with the amount of radiation administered before BMT. Two groups of mice given BMT therapy were observed for periods of 1 and 2 years, respectively. These mice were evaluated using a combination of clinical, biochemical, histochemical, and pathologic analyses. Spleen, liver, cornea, and glomerular mesangial cells showed essentially complete correction at all radiation doses. Storage was partially corrected in meninges and perivascular cells in brain, and in renal tubular epithelial cells at the higher radiation doses. Life span in BMT-treated animals was increased approximately three-fold, approaching that seen in normal mice after BMT. These results support the position that BMT has a place in the therapeutic regimen for MPS VII.

This report describes the clinical and pathologic alterations found in mice that have a recessively inherited, essentially complete deficiency of the lysosomal enzyme beta-glucuronidase. Affected animals have a shortened life span and are dysmorphic and dwarfed. Abnormal gait and decreased joint mobility correlate with glycosaminoglycan accumulation in articular tissue and cartilaginous and bony lesions result in extensive skeletal deformation. In these enzyme-deficient animals, lysosomes, distended by fine fibrillar and granular storage material, are particularly prominent in the macrophage system but also occur in other tissues including the skeletal and central nervous systems. The clinical and pathologic abnormalities in these mutant mice closely parallel those identified in humans with mucopolysaccharidoses (MPS). Therefore, these mice provide a well-defined genetic system for the analysis of the pathophysiology of mucopolysaccharidosis type VII, which has many features in common with the other MPS. The mutant mice provide an attractive animal model to test potential therapies for lysosomal storage disease.