Manganese (Mn) is both an essential biological cofactor and neurotoxicant. Disruption of Mn biology in the basal ganglia has been implicated in the pathogenesis of neurodegenerative disorders, such as parkinsonism and Huntington's disease. Handling of other essential metals (e.g. iron and zinc) occurs via complex intracellular signaling networks that link metal detection and transport systems. However, beyond several non-selective transporters, little is known about the intracellular processes regulating neuronal Mn homeostasis. We hypothesized that small molecules that modulate intracellular Mn could provide insight into cell-level Mn regulatory mechanisms. We performed a high throughput screen of 40,167 small molecules for modifiers of cellular Mn content in a mouse striatal neuron cell line. Following stringent validation assays and chemical informatics, we obtained a chemical ‘toolbox' of 41 small molecules with diverse structure-activity relationships that can alter intracellular Mn levels under biologically relevant Mn exposures. We utilized this toolbox to test for differential regulation of Mn handling in human floor-plate lineage dopaminergic neurons, a lineage especially vulnerable to environmental Mn exposure. We report differential Mn accumulation between developmental stages and stage-specific differences in the Mn-altering activity of individual small molecules. This work demonstrates cell-level regulation of Mn content across neuronal differentiation.

Olmesartan-induced enteropathy is an underreported phenomenon, first described in 2012. While olmesartan’s antihypertensive properties were confirmed early on, its association with a sprue-like enteropathy was subsequently noted. Although this association has been reported with olmesartan, there have been few reports of this association with other angiotensin-receptor blockers. We present a case of a 79-year-old male who presented with diarrhea, weight loss, jaundice, and transaminitis. Further history revealed that he had been taking olmesartan 40 mg daily for hypertension. Workup of his diarrhea and jaundice included duodenal and liver biopsies revealed findings consistent with a sprue-like enteropathy and an autoimmune hepatitis-like pattern. On discontinuation of olmesartan, his 1-month follow-up revealed significant improvement in his clinical status as well as his liver function tests. Olmesartan is an effective antihypertensive medication; however, physicians must be mindful of its side effect of causing a sprue-like enteropathy and liver injury. Patients should be counseled on discontinuing olmesartan, and they should be started on an alternative therapy for hypertension.

Inflammation of the meningeal linings of the central nervous system (CNS), also known as meningitis, is one of the serious presentations in the emergency because it carries high morbidity and mortality. The most common cause is pus-producing organisms. However, non-suppurative meningitis, termed aseptic meningitis, is another cause of meningeal inflammation. Many etiologies stand behind aseptic meningitis. Those etiologies include viral and non-viral, drug-induced, malignancy, and systemic inflammation. Druginduced aseptic meningitis is a rare type of meningitis. Although it is easily treated, it can be a challenging disease if not present in the differential diagnosis. It is commonly associated with nonsteroidal antiinflammatory drugs (NSAIDs). Nonetheless, other medications have been also reported to cause aseptic meningitis, including antibiotics. Trimethoprim-sulfamethoxazole (TMP-SMX) is one of the most prescribed antibiotics as a prophylactic and therapeutic drug due to its effectiveness and low cost. Although immunocompromised patients are at a higher risk to develop aseptic meningitis, immunocompetent patients are also at risk. Unrelated to the source of the infection, TMP-SMX carries a risk of aseptic meningitis and should be considered as an etiology in patients presenting with meningeal signs and symptoms. Hereby, we report a young immunocompetent patient who developed aseptic meningitis eight days after being prescribed TMP-SMX. Like all drug-induced aseptic meningitis, all his symptoms resolved two days after stopping the medication.

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare form of idiopathic interstitial pneumonia. The disease is characterized by fibrosis of the pleura and subpleural lung parenchyma predominantly affecting the upper lobes. Various triggers have been proposed as inciting factors in the development of the disease. Diagnosis is made clinically in conjunction with radiographic findings and histopathology when available. There are no known effective treatment options and several cases of lung transplantation have been reported. We report a case of an 86-year-old female who presented to the emergency department with worsening dyspnea and hypoxia. She had a history of unexplained pneumomediastinum and a 20 - 25 pounds unintentional weight loss over 10 months. Computed tomography (CT) of the chest without contrast revealed radiographic evidence of IPPFE. Despite symptomatic management with antibiotics, diuretics, and steroids, her condition continued to deteriorate. Unfortunately, our patient was not a candidate for a lung transplant. She was transitioned to hospice care and succumbed to her disease. IPPFE is a rare disease with an unknown prevalence. It has a median survival rate of 2 years. Usually, there is an overlap with interstitial lung diseases, making it challenging to diagnose. There are only a few cases reported in the literature, and there are currently no guidelines available on the appropriate management of this debilitating disease. We recommend more cases be reported, and further research is done to establish better criteria for diagnosis and management.

Kounis syndrome is a hypersensitivity disorder secondary to allergy or anaphylaxis that can result in acute coronary syndrome. Kounis syndrome has an increasing prevalence since its first identification in 1950. Divided into 3 subtypes, each with diagnostic criteria, the management of Kounis syndrome presents a clinical challenge. We aim to identify the pathophysiological mechanisms and review the diagnosis, epidemiology, management strategies, and future directions of Kounis syndrome. As Kounis syndrome becomes more widely recognized in the medical community, the role of diagnosis, treatment, and future immunomodulatory prevention strategies will continue to unfold.