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Hypoxia Activates Calpains in the Nerve Fibers Coating associated with Ape Retinal Explants.
ant keratinocytes. Copyright ©2020, Yale Journal of Biology and Medicine.African tick bite fever (ATBF) is a tick-borne rickettsial disease most often observed in North American and European tourists returning home from the southern portion of Africa. Ticks infected with Rickettsia africae transmit this parasitic bacterium to humans, who subsequently develop an influenza-like illness, one or more inoculation eschars, and in some cases, a cutaneous rash. Because ATBF often presents with non-specific symptoms that suggest other infectious diseases, establishing the diagnosis may be difficult. Confirmatory assays, including serology and nucleic acid amplification, may take weeks to return and cannot help with acute treatment decisions. We present a case of a previously healthy 60-year-old woman who developed an illness strongly suggestive of ATBF after a missionary trip to Zimbabwe and discuss the disease's diagnostic challenges. Our paper also reviews the epidemiology of this disease and the currently available diagnostic laboratory tests and recommended treatment options. Copyright ©2020, Yale Journal of Biology and Medicine.Diltiazem is a calcium-channel blocker commonly used for the treatment of hypertension. Common adverse effects include dizziness, headache, and edema. Fewer than 20 cases of diltiazem-associated photodistributed hyperpigmentation have been reported in the literature. Here, we present the case of a 71-year-old woman with new-onset facial hyperpigmentation 6 months after initiating treatment with diltiazem. Copyright ©2020, Yale Journal of Biology and Medicine.Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL), is characterized by malignant CD4+ skin-homing T-cells that drive formation of cutaneous patches, plaques, and/or tumors. MF's known immunogenicity makes it an ideal candidate for local immunotherapy. Recombinant human leukocyte interferon-α2 (rIFN-α2) has well-established immunomodulatory, antiproliferative, and antitumor effects; and relatively low levels of endogenous IFN-α have been observed within MF lesions. As a systemic therapy delivered via subcutaneous (SC) or intramuscular (IM) injection, rIFN-α2 has previously shown efficacy against MF. Due to high levels of toxicity associated with the systemic dosing required for improvement of disease, rIFN-α2 has had limited use in the treatment of MF. For these reasons, we sought to deliver rIFN-2 as a local immunotherapy, and herein describe two cases of MF successfully managed with intralesional injections of low-dose rIFN-α2. With limited reporting in the medical literature, intralesional injection of rIFN-α2 has shown efficacy, but with high frequency of associated systemic side effects. Towards a better tolerated, localized immunotherapy, we initiated treatment in two MF patients with low dose (0.5 MU) rIFN-α2 per injection that led to marked responses, and subsequent dosing to 1.0 MU ultimately led to complete resolution of the treated lesions without the generalized side effects observed with systemic administration of rIFN-α2. These cases suggest that low-dose intralesional rIFN-α2 may be an efficacious and well-tolerated local immunotherapy for early stage MF, providing a therapeutic option for the management of chronic, recalcitrant lesions. Copyright ©2020, Yale Journal of Biology and Medicine.Intravascular large B-cell lymphoma (IVLBCL) is a rare subset of extranodal non-Hodgkin lymphoma characterized by neoplastic lymphocytes within the lumina of small to medium-sized blood vessels. IVLBCLs are B-cell tumors that can present in essentially any organ system, including the skin. Cutaneous manifestations vary greatly and can mimic other skin disease which may delay diagnosis; in the absence of skin lesions, blind skin biopsies can be utilized for diagnosis. Early studies suggested that IVLBCL is a very aggressive lymphoma with high overall mortality rate and short survival times. However, earlier diagnosis and use of new treatment modalities have shown promise in recent studies. This case series illustrates the heterogeneity of clinical and pathologic presentations of this uncommon lymphoma. Copyright ©2020, Yale Journal of Biology and Medicine.Today, resistance to antibacterial agents is the most important problem facing public health. Pseudomonas aeruginosa is a common gram-negative bacterium and an important cause of nosocomial infections. Resistance to many antibiotics in strains of P. aeruginosa isolated from hospital settings such as cephalosporins and carbapenems have been recently reported. Therefore, the introduction of a new strategy to treat the infection of these organisms will be beneficial. In this study we determined the ability of cloxacillin to reduce Minimum Inhibitory Concentrations (MICs) of carbapenem-resistant P. aeruginosa to imipenem (IMI), meropenem (MEM), ceftazidime (CAZ), and cefepime (FEP). From 2015 to 2017, 61 non-duplicates of carbapenem-resistant P. aeruginosa were collected from clinical samples of hospitalized patients in Kerman, Iran. The MICs of the isolates to IMI, MEM, CAZ, and FEP with/without cloxacillin were determined by microbroth dilution method. The level of MIC of isolates to carbapenems (IMI and MEM) and cephalosporins (CAZ and FEP) ranged from 1-256 μg/mL and 4-1024 μg/mL alone and from 1-32 μg/mL and 1-512 μg/mL in combination with cloxacillin, respectively. The MIC showed a significant difference reduction after the addition of cloxacillin (P ≤ 0.05). Our results showed in vitro potentially of cloxacillin in reduction of MIC to IMI, MEM, CAZ, and FEP in multi-drug resistant P. aeruginosa, therefore combination of these antibiotics with cloxacillin could be beneficial for treatment of infections caused by multi-drug resistant P. aeruginosa. PLX4032 purchase Copyright ©2020, Yale Journal of Biology and Medicine.As biologic therapies become first line treatments for many inflammatory disorders, it becomes increasingly important for the practicing physician to be familiar with how these drugs function at the molecular level. This information is useful in making therapeutic decisions and helping patients understand their treatment options. It is critical to patient safety and clinical response that the molecular differences between these drugs inform prescribing practices. To this end, we present and analyze the available structural biology information about the biologics used in the treatment of psoriasis including inhibitors of tumor necrosis factor alpha (TNFα), interleukin-17 (IL-17), and interleukin-23 (IL-23). We describe and analyze the molecular surface character of known binding epitopes for medications in these classes, showing that significant differences exist in epitope location, hydrophobicity, and charge. Some of these differences can be correlated with clinical data, but our analysis ultimately points to the need for more structural information to allow for a better understanding of the structure-function relationship of biologic therapies.
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