55-year-old woman • Myalgias and progressive symmetrical proximal weakness • History of unilateral renal agenesis, type 2 diabetes, and hyperlipidemia • Dx?

► myalgias and progressive symmetrical proximal weakness ► history of unilateral renal agenesis, type 2 diabetes, and hyperlipidemia.

Speech and Language Delay in Children.

Childhood speech and language concerns are commonly encountered in the primary care setting. Family physicians are integral in the identification and initial evaluation of children with speech and language delays. Parental concerns and observations and milestone assessment aid in the identification of speech and language abnormalities. Concerning presentations at 24 months or older include speaking fewer than 50 words, incomprehensible speech, and notable speech and language deficits on age-specific testing. Validated screening tools that rely on parental reporting can serve as practical adjuncts during clinic evaluation. Early referral for additional evaluation can mitigate the development of long-term communication disorders and adverse effects on social and academic development. All children who have concerns for speech and language delays should be referred to speech language pathology and audiology for diagnostic and management purposes. Parents and caretakers may also self-refer to early intervention programs for evaluation and management of speech and language concerns in children younger than three years.

Development and evaluation of an online integrative histology module: simple design, low-cost, and improves pathology self-efficacy.

Integration of core concepts is an important aspect of medical curriculum enhancement. Challenges to improving integration include the risk of curtailing the basic sciences in the process and the push to decrease contact hours in medical curricula. Self-paced learning tools can be developed that deliberately relate basic and clinical sciences to aid students in making interdisciplinary connections. The purpose of this project was to develop, implement, and evaluate a self-paced learning module that would be applicable to integration of different disciplines in medical education. The module was intended to improve integration between histology and anatomic pathology before a respiratory pathology laboratory session. Qualtrics XM, a survey software commonly available at educational institutions, was used in a novel manner to create the module. Module activities included pre- and post-module quizzes; four short videos emphasizing normal histological features and recalling associated pathologies; three categorization activities designed for students to recognize normal versus abnormal characteristics of lung specimens; and post-activity feedback. Preliminary data from first-year medical students showed that post-module quiz scores were significantly higher than pre-module quiz scores (p < 0.001) and that module users' pre-laboratory pathology self-efficacy was significantly higher than non-users (p < 0.05). These data suggest that module use facilitated short-term knowledge gain and improved pathology self-efficacy before the laboratory session. Online modules can be developed affordably using Qualtrics XM to integrate anatomical sciences with other disciplines, while providing students interactive learning resources without increasing contact hours. The module presented in this report focused on normal versus abnormal morphology, guiding students through recognizing the continuum from healthy to disease states before learning about the pathologies more in depth. A similar module design would likely be effective in integrating other disciplines in medicine, especially in disciplines that require recognition of changes in morphology.

Rasburicase-induced haemolysis and methemoglobinemia: an ongoing issue.

We report a case of a 91-year-old Caucasian woman with a history of chronic lymphocytic leukaemia who developed acute hypoxic respiratory failure (AHRF) requiring intubation for less than 24 hours after receiving rasburicase. Laboratory workup was significant for methemoglobinemia and acute anaemia, and blood film demonstrated evidence of oxidative haemolysis with bite cells. The patient was given a presumptive diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency and was managed conservatively with successful resolution of AHRF and stabilisation of haemoglobin level. Seven days after admission, she passed away due to subsequent complications; hence, follow-up G6PD level could not be obtained. Haemolytic anaemia and methemoglobinemia in the setting of recent rasburicase administration should raise clinical suspicion for G6PD deficiency. In non-emergent cases, patients should be screened prior to receiving rasburicase regardless of risk factors. Because rasburicase is often needed emergently, patients at high risk of tumour lysis syndrome should be screened early for G6PD deficiency.

Immunology of Gut-Bone Signaling.

In recent years a link between the gastrointestinal tract and bone health has started to gain significant attention. Dysbiosis of the intestinal microbiota has been linked to the pathology of a number of diseases which are associated with bone loss. In addition modulation of the intestinal microbiota with probiotic bacteria has revealed to have both beneficial local and systemic effects. In the present chapter, we discuss the intestinal and bone immune systems, explore how intestinal disease affects the immune system, and examine how these pathologic changes could adversely impact bone health.

Temporal and regional intestinal changes in permeability, tight junction, and cytokine gene expression following ovariectomy-induced estrogen deficiency.

Estrogen deficiency that occurs during menopause is associated with wide-ranging consequences, including effects on the gastrointestinal system. Although previous studies have implicated a role for estrogen in modulating colonic permeability and inflammatory gene expression, the kinetics of these changes following loss of estrogen and whether they are intestinal region specific are unknown. To test this, we performed sham or ovariectomy (OVX) surgery in BALB/c mice and examined permeability (in vivo and ex vivo) and gene expression changes in the duodenum, jejunum, ileum, and colon at 1, 4, and 8 weeks postsurgery. In vivo permeability, assessed by FITC-dextran gavage and subsequent measures of serum levels, indicated that OVX significantly increased whole intestinal permeability 1 week postsurgery before returning to sham levels at 4 and 8 weeks. Permeability of individual intestinal sections, measured ex vivo by Ussing chambers, revealed specific regional and temporal responses to OVX, with the most dynamic changes exhibited by the ileum. Analysis of gene expression, by qPCR and by mathematical modeling, revealed an OVX-specific effect with tight junction and inflammatory gene expression elevated and suppressed with both temporal and regional specificity. Furthermore, ileal and colonic expression of the tight junction protein occludin was found to be significantly correlated with expression of TNFα and IL-1ß Together, our studies reveal previously unappreciated effects of estrogen deficiency in specific intestinal segments and further demonstrate temporal links between estrogen deficiency, inflammatory genes, and intestinal permeability.

Estrogen Deficiency Exacerbates Type 1 Diabetes-Induced Bone TNF-α Expression and Osteoporosis in Female Mice.

Estrogen deficiency after menopause is associated with rapid bone loss, osteoporosis, and increased fracture risk. Type 1 diabetes (T1D), characterized by hypoinsulinemia and hyperglycemia, is also associated with bone loss and increased fracture risk. With better treatment options, T1D patients are living longer; therefore, the number of patients having both T1D and estrogen deficiency is increasing. Little is known about the mechanistic impact of T1D in conjunction with estrogen deficiency on bone physiology and density. To investigate this, 11-week-old mice were ovariectomized (OVX), and T1D was induced by multiple low-dose streptozotocin injection. Microcomputed tomographic analysis indicated a marked reduction in trabecular bone volume fraction (BVF) in T1D-OVX mice (~82%) that was far greater than the reductions (~50%) in BVF in either the OVX and T1D groups. Osteoblast markers, number, and activity were significantly decreased in T1D-OVX mice, to a greater extent than either T1D or OVX mice. Correspondingly, marrow adiposity was significantly increased in T1D-OVX mouse bone. Bone expression analyses revealed that tumor necrosis factor (TNF)-α levels were highest in T1D-OVX mice and correlated with bone loss, and osteoblast and osteocyte death. In vitro studies indicate that estrogen deficiency and high glucose enhance TNF-α expression in response to inflammatory signals. Taken together, T1D combined with estrogen deficiency has a major effect on bone inflammation, which contributes to suppressed bone formation and osteoporosis. Understanding the mechanisms/effects of estrogen deficiency in the presence of T1D on bone health is essential for fracture prevention in this patient population.