Positive Influences and Challenges for the Deaf Community Navigating Access to HIV Information, Testing, and Treatment in Kampala, Uganda: A Qualitative Study.

Although sub-Saharan Africa has the highest HIV burden globally, few studies have investigated disabilities and HIV in this region. We conducted a secondary analysis of text data from in-depth interviews (2014-2015) to describe HIV perceptions among a subsample of 73 deaf individuals participating in the Crane survey, Kampala, Uganda. Being deaf was defined as being profoundly or functionally deaf, having deafness onset 5 + years ago, and preferring sign language to communicate. Among participants ever tested for HIV (47%), most (88%) had a negative test. Thematic analysis revealed overcoming challenges/barriers followed by socioeconomic status, support systems, HIV, stigma, abuse, and health conditions as major themes. An unanticipated finding was the role of sex work to support basic living needs. The data showed related themes among participants, suggesting a complex context in which deaf participants experience HIV prevention and treatment. It is important to tailor HIV interventions for deaf and disabled persons.

Management of Pregnancy in Lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that primarily affects women of childbearing age. Pregnancy-related morbidity and mortality are well described in SLE; however, better management of disease activity throughout the disease course have minimized periods of disease activity and damage accrual, making pregnancy more feasible and desirable. A growing body of literature has defined risk factors for adverse pregnancy outcomes in patients with SLE, and coordinated medical and obstetric management has allowed most patients with SLE to safely achieve full-term pregnancies by timing pregnancy to maximal disease quiescence and use of pregnancy-compatible medications from preconception through lactation.

Spiradenoma With Adenoid Cystic Carcinoma-Like Features.

Spiradenoma is a benign cutaneous adnexal neoplasm that characteristically presents as a painful dermal nodule, often on the head or trunk. It has a distinct histologic phenotype and management involves surgical excision with low risk of recurrence. In comparison, adenoid cystic carcinoma (ACC) is a low-grade malignancy manifesting as an often painless subcutaneous mass with potential for local invasion, perineural extension, and high rates of recurrence after excision. We report the case of a 63-year-old male patient with a recurrent, painful hematoma-like cyst overlying the left lower extremity tibial tuberosity. A firm nodule was located at the base of the cyst, which was histologically consistent with spiradenoma. Interestingly, the lesion contained multifocal ACC-like components composed of epithelial basaloid cells surrounding pseudocystic structures filled with mucinous material. The ACC-like components did not demonstrate infiltration or perineural invasion. To the best of our knowledge, this is the second publication in the English literature regarding spiradenoma with an ACC-like pattern. Although a benign entity, knowledge of this morphological variant of spiradenoma is essential for diagnostic accuracy in these cases. If a limited biopsy captures only the ACC-like component of a spiradenoma, the lesion may be incorrectly diagnosed as ACC.

"Puffy shirt appearance": Cell crowding at low magnification may represent nevoid melanoma.

BACKGROUND: Melanoma, particularly nevoid melanoma, can masquerade as benign. Helpful differentiating features include nuclear pleomorphism, atypia, prominent nucleoli, absent maturation, and increased mitotic figures. These can be subtle and easily missed unless carefully sought. Thus, the "puffy shirt appearance" concept was born from a Seinfeld episode in which the namesake character unintentionally agreed to wear a pirate-like puffy shirt. Consequently, he found himself out of place, sporting an outfit with "too much shirt in too little space". Similarly, at low-power, nevoid melanoma appears to have "too many cells in too little space". This is more pronounced and easier to appreciate when there is an associated nevus, where crowded, subtly malignant melanocytes stand out from the evenly distributed, more spaced out benign melanocytes. METHODS: Twelve practicing dermatopathologists familiar with the puffy shirt concept in the context of melanoma were surveyed. RESULTS: Hundred percent of participants found it most helpful as a triaging tool, prompting additional work up including higher magnification evaluation, additional levels, consultation, and/or immunohistochemistry. CONCLUSIONS: The crowded cells in the "puffy shirt appearance" catch the eye and should provoke a more thorough inspection of the lesion. This sign is not pathognomonic for melanoma, but prompts more careful evaluation and helps prevent misdiagnosis.

Kikuchi-Fujimoto Disease: An Atypical Presentation of a Rare Disease.

Kikuchi-Fujimoto disease (KFD), or necrotizing histiocytic lymphadenitis, is a rare cause of lymphadenopathy and fever. Although the clinical course is usually benign, KFD is often mistaken for malignancy or infection. Recognition of typical and atypical cases of KFD is necessary to avoid unnecessary interventions. Here we report an atypical presentation of KFD with diffuse lymphadenopathy and leukocytosis associated with high levels of circulating Epstein-Barr viral DNA.

Corrigendum: Leukemia cutis as the presenting symptom of acute myeloid leukemia: report of three cases.

The original article was published on July19, 2017 and corrected on June 15, 2018.The revised version of the article adds appropriate in-text references to Figures 3B, C and 5B, C, and correctly renumbers the list of References. The changes appear in the revised online PDF copy of this article.

Leukemia cutis as the presenting symptom of acute myeloid leukemia: report of three cases.

Leukemia cutis (LC), a rare cutaneous manifestation of leukemia, can precede, follow, occur concurrently with, or present in the absence of (aleukemic) systemic leukemia. Leukemia cutis is especially rare as the presenting symptom of leukemia and is associated with a poor prognosis. Although more commonly seen in acute leukemias of myeloid and monocytic lineage, lymphocytic/lymphoblastic leukemias can also involve the skin. Three cases of LC presented with diverse skin lesions ranging from an erythematous rash to violaceous macules and papules to subcutaneous nodules. One case clinically mimicked fixed drug eruption. All the patients had acute myeloid leukemia (AML). Lesions showed two overarching histologic patterns: atypical perivascular infiltrate or nodular dermal histiocytoid infiltrate. Our cases expressed myeloperoxidase (MPO), a helpful marker to distinguish myeloid from non-myeloid cells, and CD68, a monocytic marker frequently expressed in cutaneous AML. CD14, a marker of monocyte maturity, was negative. In the absence of systemic leukemia, common diagnostic tools for hematologic malignancies such as bone marrow biopsy and flow cytometry are non-contributory, making morphologic and immunohistochemical analysis of the skin lesions key to diagnosis.

Human Papillomavirus-Driven Squamous Lesions: High-Risk Genotype Found in Conjunctival Papillomas, Dysplasia, and Carcinoma.

BACKGROUND: Human papillomavirus (HPV) is a causative agent for intraepithelial squamous neoplasms, particularly on mucosal surfaces. HPV has a well-established association with squamous cell carcinoma (SCC) of the oropharynx and genital tract, and recent studies suggest a potential role in ocular and periocular squamous neoplasms. Multiple high-risk HPV genotypes are associated with histologically similar squamous neoplasms, and some HPV genotypes have been differentially associated with high- or low-grade lesions. METHODS: Squamous lesions were screened with immunohistochemical markers p16 and Ki-67 to compare expression in conjunctival papillomas (n = 21) to papillomas with high-grade dysplasia, SCC in situ, and invasive SCC (n = 40). Polymerase chain reaction was performed using the Roche COBAS HPV assay to identify the 14 most common high-risk HPV genotypes. RESULTS: Compared with squamous papillomas, the lesions showing high-grade dysplasia or worse expressed p16 with greater intensity and in a greater percentage of the lesion. A trend toward mild Ki-67 expression in papillomas versus marked Ki-67 expression in high-grade squamous lesions was also observed. HPV-16 was present in 7 of the SCC in situ and invasive SCC lesions but none of the papillomas. CONCLUSIONS: HPV may have an important role in squamous lesions of the conjunctiva. In addition to positive polymerase chain reaction results, strong and diffuse p16 expression with marked Ki-67 is strongly suggestive of an HPV-driven lesion.

The effects of the Bethesda System 2014 on endometrial cell reporting and follow-up endometrial biopsies in women 45 years of age and over.

INTRODUCTION: The Bethesda System (TBS) guidelines for reporting the presence of endometrial cells on Papanicolaou tests increased the reporting age from 40 (TBS 2001) to 45 (TBS 2014) years. Exfoliated endometrial cells (EMC) are usually a normal finding. Nevertheless, benign-appearing EMC occasionally correspond to endometrial hyperplasia or malignancy, especially in older, postmenopausal women. This study assesses the impact of this age cutoff change. MATERIALS AND METHODS: This retrospective review compares endometrial biopsies following TBS 2001 and TBS 2014. Papanicolaou tests with EMC reported in women older than age 40 or 45 years were correlated with follow-up endometrial biopsies performed between May 25, 2014, to May 26, 2015, and May 27, 2015, to May 26, 2016, respectively. RESULTS: The number of reported EMC declined from 770 to 492 (a 36.1% decrease). The follow-up endometrial biopsy rate for Papanicolaou tests reporting EMC using TBS 2001 was 13.6% (105 of 770) versus TBS 2014 at 13.8% (68 of 492; P = 0.92). For TBS 2001, 15% of women aged 45 and older had follow-up biopsies (65 of 434; P = 0.62). Most follow-up biopsies showed benign endometrium. In the TBS 2001 group, 1 biopsy showed malignancy and another showed complex hyperplasia with atypia. Both patients were older than 45 years. The TBS 2014 group contained 1 biopsy of malignancy and 1 with simple hyperplasia with focal atypia. CONCLUSIONS: The implementation of TBS 2014 reduced the frequency of reporting benign-appearing endometrial cells. The follow-up biopsy rate has remained essentially the same, but the total number of biopsies performed decreased, with a similar low yield of significant abnormalities.

Scapholunate and perilunate injuries in the athlete.

PURPOSE OF THE REVIEW: Scapholunate and perilunate injuries can be difficult to diagnose and treat in the athlete. In this review article, we present the mechanism of injury, evaluation, management, and outcomes of treatment for these injuries. RECENT FINDINGS: Acute repair of dynamic scapholunate ligament injuries remains the gold standard, but judicious use of a wrist splint can be considered for the elite athlete who is in season. The treatment of static scapholunate ligament injury remains controversial. Newer SL reconstructive techniques that aim to restore scapholunate function without compromising wrist mobility as much as tenodesis procedures show promise in athlete patients. Acute injuries to the scapholunate ligament are best treated aggressively in order to prevent the sequelae of wrist arthritis associated with long-standing ligamentous injury. Acute repair is favored. Reconstructive surgical procedures to manage chronic scapholunate injury remain inferior to acute repair. The treatment of lunotriquetral ligament injuries is not well defined.

Post-traumatic Stress Disorder and Magnetic Resonance Imaging.

Although post-traumatic stress disorder (PTSD) is not fully understood, considerable research has gone into studying anatomical changes in the brain that take place with this condition. Magnetic resonance (MR) imaging can demonstrate changes in the volume of numerous brain regions, and functional MR imaging shows changes in activation when subjects are exposed to trauma-related stimuli. This article reviews current research findings on PTSD-associated brain changes and behavioral effects and discusses how PTSD affects patients of different ages.

Significantly reduced lymphadenopathy, salivary gland infiltrates and proteinuria in MRL-lpr/lpr mice treated with ultrasoluble curcumin/turmeric: increased survival with curcumin treatment.

OBJECTIVES: Commercial curcumin (CU), derived from food spice turmeric (TU), has been widely studied as a potential therapeutic for a variety of oncological and inflammatory conditions. Lack of solubility/bioavailability has hindered curcumin's therapeutic efficacy in human diseases. We have solubilised curcumin in water applying heat/pressure, obtaining up to 35-fold increase in solubility (ultrasoluble curcumin (UsC)). We hypothesised that UsC or ultrasoluble turmeric (UsT) will ameliorate systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS)-like disease in MRL-lpr/lpr mice. METHODS: Eighteen female MRL-lpr/lpr (6 weeks old) and 18 female MRL-MpJ mice (6 weeks old) were used. Female MRL-lpr/lpr mice develop lupus-like disease at the 10th week and die at an average age of 17 weeks. MRL-MpJ mice develop lupus-like disease around 47 weeks and typically die at 73 weeks. Six mice of each strain received autoclaved water only (lpr-water or MpJ-water group), UsC (lpr-CU or MpJ-CU group) or UsT (lpr-TU or MpJ-TU group) in the water bottle. RESULTS: UsC or UsT ameliorates SLE in the MRL-lpr/lpr mice by significantly reducing lymphoproliferation, proteinuria, lesions (tail) and autoantibodies. lpr-CU group had a 20% survival advantage over lpr-water group. However, lpr-TU group lived an average of 16 days shorter than lpr-water group due to complications unrelated to lupus-like illness. CU/TU treatment inhibited lymphadenopathy significantly compared with lpr-water group (p=0.03 and p=0.02, respectively) by induction of apoptosis. Average lymph node weights were 2606±1147, 742±331 and 385±68 mg, respectively, for lpr-water, lpr-CU and lpr-TU mice. Transferase dUTP nick end labelling assay showed that lymphocytes in lymph nodes of lpr-CU and lpr-TU mice underwent apoptosis. Significantly reduced cellular infiltration of the salivary glands in the lpr-TU group compared with the lpr-water group, and a trend towards reduced kidney damage was observed in the lpr-CU and lpr-TU groups. CONCLUSIONS: These studies show that UsC/UsT could prove useful as a therapeutic intervention in SLE/SS.

Chloroquine is a zinc ionophore.

Chloroquine is an established antimalarial agent that has been recently tested in clinical trials for its anticancer activity. The favorable effect of chloroquine appears to be due to its ability to sensitize cancerous cells to chemotherapy, radiation therapy, and induce apoptosis. The present study investigated the interaction of zinc ions with chloroquine in a human ovarian cancer cell line (A2780). Chloroquine enhanced zinc uptake by A2780 cells in a concentration-dependent manner, as assayed using a fluorescent zinc probe. This enhancement was attenuated by TPEN, a high affinity metal-binding compound, indicating the specificity of the zinc uptake. Furthermore, addition of copper or iron ions had no effect on chloroquine-induced zinc uptake. Fluorescent microscopic examination of intracellular zinc distribution demonstrated that free zinc ions are more concentrated in the lysosomes after addition of chloroquine, which is consistent with previous reports showing that chloroquine inhibits lysosome function. The combination of chloroquine with zinc enhanced chloroquine's cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine's anticancer activity.

M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway.

Tissue remodeling processes critically depend on the timely removal and remodeling of preexisting collagen scaffolds. Nevertheless, many aspects related to the turnover of this abundant extracellular matrix component in vivo are still incompletely understood. We therefore took advantage of recent advances in optical imaging to develop an assay to visualize collagen turnover in situ and identify cell types and molecules involved in this process. Collagen introduced into the dermis of mice underwent cellular endocytosis in a partially matrix metalloproteinase-dependent manner and was subsequently routed to lysosomes for complete degradation. Collagen uptake was predominantly executed by a quantitatively minor population of M2-like macrophages, whereas more abundant Col1a1-expressing fibroblasts and Cx3cr1-expressing macrophages internalized collagen at lower levels. Genetic ablation of the collagen receptors mannose receptor (Mrc1) and urokinase plasminogen activator receptor-associated protein (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies a key role of M2-like macrophages in this process.

The non-phagocytic route of collagen uptake: a distinct degradation pathway.

The degradation of collagens, the most abundant proteins of the extracellular matrix, is involved in numerous physiological and pathological conditions including cancer invasion. An important turnover pathway involves cellular internalization and degradation of large, soluble collagen fragments, generated by initial cleavage of the insoluble collagen fibers. We have previously observed that in primary mouse fibroblasts, this endocytosis of collagen fragments is dependent on the receptor urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180. Others have identified additional mechanisms of collagen uptake, with different associated receptors, in other cell types. These receptors include ß1-integrins, being responsible for collagen phagocytosis, and the mannose receptor. We have now utilized a newly developed monoclonal antibody against uPARAP/Endo180, which down-regulates the receptor protein level on treated cells, to examine the role of uPARAP/Endo180 as a mediator of collagen internalization by a wide range of cultured cell types. With the exception of macrophages, all cells that proved capable of efficient collagen internalization were of mesenchymal origin and all of these utilized uPARAP/Endo180 for their collagen uptake process. Macrophages internalized collagen in a process mediated by the mannose receptor, a protein belonging to the same protein family as uPARAP/Endo180. ß1-Integrins were found not to be involved in the endocytosis of soluble collagen, irrespectively of whether this was mediated by uPARAP/Endo180 or the mannose receptor. This further distinguishes these pathways from the phagocytic uptake of particulate collagen.

Distinct Kinesin-14 mitotic mechanisms in spindle bipolarity.

Kinesin-like proteins are integral to formation and function of a conserved mitotic spindle apparatus that directs chromosome segregation and precedes cell division. Ubiquitous to the mechanism of spindle assembly and stability are balanced Kinesin-5 promoting and Kinesin-14 opposing forces. Distinct Kinesin-14 roles in bipolarity in eukaryotes have not been shown, but are suggested by gamma-tubulin-based pole interactions that affect establishment and by microtubule cross-linking and sliding that maintain bipolarity and spindle length. Distinct roles also imply specialized functional domains. By cross-species analysis of compatible mechanisms in establishing mitotic bipolarity we demonstrate that Kinesin-14 human HSET (HsHSET) functionally replaces Schizosaccharomyces pombe Pkl1 and its action is similarly blocked by mutation in a Kinesin-14 binding site on gamma-tubulin. Drosophila DmNcd localizes preferentially to bundled interpolar microtubules in fission yeast and does not replace SpPkl1. Analysis of twenty-six Kinesin-14 derivatives, including Tail, Stalk or Neck-Motor chimeras, for spindle localization, spindle assembly and mitotic progression defined critical domains. The Tail of SpPkl1 contains functional elements enabling its role in spindle assembly that are distinct from but transferable to DmNcd, whereas HsHSET function utilizes both Tail and Stalk features. Our analysis is the first to demonstrate distinct mechanisms between SpPkl1 and DmNcd, and reveal that HsHSET shares functional overlap in spindle pole mechanisms.