Modelling drug adsorption in metal-organic frameworks: the role of solvent.

Solvent plays a key role in biological functions, catalysis, and drug delivery. Metal-organic frameworks (MOFs) due to their tunable functionalities, porosities and surface areas have been recently used as drug delivery vehicles. To investigate the effect of solvent on drug adsorption in MOFs, we have performed integrated computational and experimental studies in selected biocompatible MOFs, specifically, UiO-AZB, HKUST-1 (or CuBTC) and NH2-MIL-53(Al). The adsorption of three drugs, namely, 5-fluorouracil (5-FU), ibuprofen (IBU), and hydroxyurea (HU) were performed in the presence and absence of the ethanol. Our computational predictions, at 1 atmospheric pressure, showed a reasonable agreement with experimental studies performed in the presence of ethanol. We find that in the presence of ethanol the drug molecules were adsorbed at the interface of solvent and MOFs. Moreover, the computationally calculated adsorption isotherms suggested that the drug adsorption was driven by electrostatic interactions at lower pressures (<10-4 Pa). Our computational predictions in the absence of ethanol were higher compared to those in the presence of ethanol. The MOF-adsorbate interaction (U HA) energy decreased with decrease in the size of a drug molecule in all three MOFs at all simulated pressures. At high pressure the interaction energy increases with increase in the MOFs pore size as the number of molecules adsorbed increases. Thus, our research shows the important role played by solvent in drug adsorption and suggests that it is critical to consider solvent while performing computational studies.

Disseminated Tuberculosis Presenting as Chronic Orchiepididymitis in a Military Trainee: A Case Report and Review of the Literature.

Orchiepididymitis is a clinical diagnosis. The acute form secondary to sexually transmitted or enteric pathogens is well known to primary care providers. However, chronic orchiepididymitis may be secondary to genitourinary tuberculosis (TB), and physicians in countries with a low prevalence of TB might not consider it in their differential diagnosis. Indeed, cognitive errors, such as anchoring or availability bias, may contribute to a delayed diagnosis of genitourinary TB. We present a case of chronic orchiepididymitis as a result of disseminated TB in a Cameroonian male who was visiting the United States for military training. He experienced diagnostic delay and was ultimately diagnosed by orchiectomy. Early consideration of a diagnosis of TB for chronic or recurrent orchiepididymitis in a patient with epidemiologic risk factors is of utmost importance because delayed diagnosis could lead to organ loss.

Frozen Section Diagnostic Pitfalls of Sertoli-Leydig Cell Tumor with Heterologous Elements.

A woman in her sixth decade presented with several months of abdominal cramping, decreased appetite, bloating, and increased constipation. Radiologic imaging revealed a 28 cm, multilocular, heterogeneous cystic neoplasm involving the right adnexa. An intraoperative frozen section showed mucinous glandular epithelium, with and without foci of goblet cells, embedded in apparent ovarian stroma. The findings were concerning at least borderline mucinous cystadenoma with possible invasion. Subsequent surgical management and staging were performed. Permanent sections showed a moderately to poorly differentiated Sertoli-Leydig cell tumor (SLCT) with retiform foci and heterologous elements. The discrepancy between frozen and permanent sections was attributable to solely sampling a focus of heterologous elements during intraoperative consultation. The rarity of SLCT and even rarer presence of both heterologous and retiform elements make this concerning frozen section diagnostic pitfall.

A Case of Spontaneously Improving Secondary Hemophagocytic Lymphohistiocytosis in an Adult Associated with T-Cell Histiocyte-Rich Large B-Cell Lymphoma.

Secondary hemophagocytic lymphohistiocytosis (HLH) in adults is a rare, often fatal syndrome characterized by widespread immune dysregulation. It is seen as a complication of infections, autoimmune diseases, and malignancies. Among the malignancy-related causes, aggressive T-cell or NK-cell neoplasms are most notable, while B-cell lymphomas are less commonly implicated. We present the case of a 32-year-old male transferred to our facility with concern for HLH. During the first week of his hospitalization, his diagnosis was confirmed and the patient demonstrated spontaneous improvement in his symptoms prompting us to delay therapy while searching for a primary cause. In the second week, the patient deteriorated, leading us to initiate steroid monotherapy in the absence of a cause for his HLH. Meanwhile, pathology results from an excisional lymph node biopsy confirmed a diagnosis of T-cell/histiocyte-rich large B-cell lymphoma (TCHRLBCL). Subsequently, we initiated therapy with dose-adjusted R-EPOCH. The patient achieved a complete remission of both HLH and TCHRLBCL as well as a complete return to his prior functional status. In our review of the literature, this represents only the second documented case of HLH associated with TCHRLBCL and the only documented case of an adult experiencing significant spontaneous recovery in this context.

Hoyeraal-Hreidarsson Syndrome due to PARN Mutations: Fourteen Years of Follow-Up.

BACKGROUND: Hoyeraal-Hreidarsson syndrome is a dyskeratosis congenita-related telomere biology disorder that presents in infancy with intrauterine growth retardation, immunodeficiency, and cerebellar hypoplasia in addition to the triad of nail dysplasia, skin pigmentation, and oral leukoplakia. Individuals with Hoyeraal-Hreidarsson syndrome often develop bone marrow failure in early childhood. Germline mutations in DKC1, TERT, TINF2, RTEL1, ACD, or PARN cause about 60% of individuals with Hoyeraal-Hreidarsson syndrome. PATIENT DESCRIPTION: We describe 14 years of follow-up of an individual with Hoyeraal-Hreidarsson syndrome who initially presented as an infant with intrauterine growth retardation, microcephaly, and central nervous system calcifications. He was diagnosed with Hoyeraal-Hreidarsson syndrome at age 6 years and had a complicated medical history including severe developmental delay, cerebellar hypoplasia, esophageal and urethral stenosis, hip avascular necrosis, immunodeficiency, and bone marrow failure evolving to myelodysplastic syndrome requiring hematopoietic cell transplantation at age 14 years. He had progressive skin pigmentation, oral leukoplakia, and nail dysplasia leading to anonychia. Whole exome sequencing identified novel biallelic variants in PARN. CONCLUSIONS: This patient illustrates that the constellation of intrauterine growth retardation, central nervous system calcifications, and cerebellar hypoplasia, esophageal or urethral stenosis, and cytopenias, in the absence of congenital infection, may be due to Hoyeraal-Hreidarsson syndrome. Early diagnosis of Hoyeraal-Hreidarsson syndrome is important to optimize medical management and provide genetic counseling.

Asteatotic eczema in hypoesthetic skin: a case series.

IMPORTANCE: Asteatotic eczema (eczema craquelé, xerotic eczema) occurs most frequently in areas of dehydrated skin, most often during the winter months when decreased humidity results in increased water loss from the stratum corneum. We present 5 cases in which asteatotic eczema was found outside of its normal distribution, within desensitized skin and scars. OBSERVATIONS: Five patients with a history of trauma and scar formation presented with erythematous, dry plaques with fine crackling involving hypoesthetic skin. Each of the 5 patients had classic asteatotic eczema skin findings, the only commonality being hypoesthesia. Borders of the hypoesthetic skin were identified using light touch and compared with the regions affected by asteatotic eczema. In all cases, the skin affected by asteatotic eczema was within the hypoesthetic areas. CONCLUSIONS AND RELEVANCE: Asteatotic eczema developing on skin with altered sensation is an underreported condition. Prompt recognition and treatment may lead to a more efficient patient encounter and alleviate unnecessary patient stress.