The effect of photobiomodulation on histamine and Mucuna pruriens-induced pruritus, hyperknesis and alloknesis in healthy volunteers: A double-blind, randomized, sham-controlled study.

BACKGROUND: Photobiomodulation, also referred to as Low-Level Light Therapy (LLLT), has emerged as a promising intervention for pruritus, a prevalent and often distressing symptom. OBJECTIVES: This study investigated the efficacy of low-level light therapy (LLLT) in alleviating pruritus, hyperknesis, and alloknesis induced by histamine and Mucuna pruriens. METHODS: In a double-blind, randomized, sham-controlled trial with a split-body design, healthy volunteers underwent 6 minutes of LLLT and sham treatments in separate upper back quadrants. The histamine model was applied to the upper quadrants, and Mucuna pruriens to the lower quadrants. Pruritus intensity, alloknesis, hyperknesis, flare area, and skin temperature were measured pre and post treatment. RESULTS: Seventeen individuals (eight females, nine males) participated in the study. In the histamine model, LLLT notably reduced itch intensity (difference = 13.9 (95% CI: 10.5 - 17.4), p = 0.001), alloknesis (difference = 0.80 (95% CI: 0.58-1.02), p = 0.001), and hyperknesis (difference = 0.48 (95% CI: 0.09-0.86), p = 0.01). Skin temperature changes were not significantly different between the two groups (difference = -2.0 (95% CI: -6.7-2.6), p = 0.37). For the Mucuna pruriens model, no significant differences were observed in any measures, including itch intensity (difference = 0.8 (95% CI: -2.3 - 3.8), p = 0.61) hyperknesis (difference = 0.08 (95% CI: -0.06-0.33), p = 0.16) and alloknesis (difference = 0. 0.09 (95% CI: -0.08-0.256), p = 0.27). CONCLUSIONS: LLLT effectively reduced histamine-induced pruritus, alloknesis, and hyperknesis; however, LLLT was ineffective against Mucuna pruriens-induced pruritus. Further investigations are required to determine LLLT's effectiveness of LLLT in various pruritus models.

Abundance of the Organic Anion-transporting Polypeptide OATP4A1 in Early-Stage Colorectal Cancer Patients: Association With Disease Relapse.

The abundance of OATP4A1 in colorectal cancer (CRC) might be related to tumor progression. This was studied by immunohistochemistry on paraffin-embedded samples obtained from 178 patients (43 patients with a relapse within 5 y) with early-stage CRC. Positivity for OATP4A1 in tumor cells and noncancerous mucosal cells was proved by double-immunofluorescence staining with antibodies against OATP4A1 and keratin 8, whereas antibodies against appropriate CD markers were used to identify immune cells. Automated microscopic image analysis was used to measure the percentage of OATP4A1-positive cells and OATP4A1 staining intensity in tumor, immune, and adjacent normal-looking mucosal cells separately, as well as in the mucosal and immune cells of 14 nonmalignant tissue samples. In CRC the percentage of OATP4A1-positive cells, but not staining intensity, was significantly higher in tumor and mucosal cells adjacent to the tumor compared to the mucosa of nonmalignant samples (P<0.001 each). No difference was registered between immune cells in malignant and nonmalignant samples. Importantly, high levels of OATP4A1 in immune (odds ratio, 0.73; confidence interval, 0.63-0.85; P<0.001), and tumor cells (odds ratio, 0.79; confidence interval, 0.69-0.91; P<0.001) are significantly associated with a low risk of recurrence and also significantly enhance the discriminative power of other clinical parameters [such as International Union Against Cancer (UICC), adjuvant therapy, localization of the primary tumor] of the risk of relapse (receiver operating characteristics analysis; P=0.002). Using an advanced digital microscopic quantification procedure, we showed that OATP4A1 abundance is negatively associated with tumor recurrence in early-stage CRC. This digital scoring procedure may serve as a novel tool for the assessment of potential prognostic markers in early-stage CRC.

Introduction: transnational lesbian cultures.

This special issue examines the transnational shape and shaping of lesbian lives and cultures in and across China, India, the United Kingdom, and the United States. It uses the expression "transnational lesbian cultures" to suggest that despite sometimes radically different sociopolitical and cultural contexts, the lived experiences of same-sex desire and their emotional attachments create particular affinities between women who love women, affinities that reach across the distinct cultural and social contexts that shape them. The articles brought together explore lesbian subcultures, film, graphic novels, music, and online intimacies. They show that as a cultural and political signifier and as an analytical tool, lesbian troubles and complicates contemporary sexual politics, not least by revealing some of the gendered structures that shape debates about sexuality in a range of critical, cultural and political contexts. While the individual pieces cover a wide range of issues and concerns-which are often highly specific to the historical, cultural, and political contexts they discuss-together they tell a story about contemporary transnational lesbian culture: one that is marked by intricate links between norms and their effects and shaped by the efforts to resist denial, discrimination, and sometimes even active persecution.

Vital lines drawn from books: difficult feelings in Alison Bechdel's Fun Home and Are You My Mother?

This article examines the representation of a transnational archive of queer books in Alison Bechdel's graphic memoirs Fun Home and Are You My Mother? for the insights it provides into the role of reading in making sense of the often difficult "felt experiences" of lesbian life. In both memoirs, books serve an important narrative function in the portrayal of Alison's lesbian identification and its complex emotional entanglements with the lives of parents who are trapped-killed even, in the case of the father-in the wastelands of patriarchy and heterosexual expectation. The article argues that in this complex family dynamic in which "sexual identity" itself is a problem and emotions remain largely unspoken, books act as fragile conduits of feelings, shaping familial relationships even as they allow Alison to contextualize her life in relation to historical events and social norms. Reading books allows her to understand the apparently U.S.-specific history of her family in relation to a wider queer history in the West.

Primary cutaneous follicle center lymphoma -'crosti lymphoma': what can we learn?

In 1951, Crosti reported on seven patients with 'reticulo-histiocytoma of the back' who presented with figurate erythematous plaques and nodules on the back or lateral trunk. Reticulo-histiocytoma of the back was later classified as a primary cutaneous follicle center lymphoma (PCFCL). A definitive diagnosis of the condition is frequently delayed because of a relative lack of clinical symptoms and difficulties in interpretation of the histologic findings. Indeed, a number of primary cutaneous B-cell lymphomas have been mislabeled as pseudolymphomas in the past. We present a case of PCFCL that initially demonstrated predominantly small T lymphocytes on histology. These findings were interpreted as an inflammatory pseudolymphomatous reaction. However, small lymphocytes, whether B or T cells, in early lesions of cutaneous B-cell lymphomas should not automatically be considered 'reactive.' Persistent antigenic stimulation of lymphocytes in a neoplastic process or by an antigen, for example, Borrelia burgdorferi, can lead to transformation and cell division with development of large blast cells. In our patient, the initial scarcity of B lymphocytes also led to further diagnostic difficulties. Although the association of primary cutaneous B-cell lymphoma with Borrelia infection is known, there are still difficulties in differentiating the condition from pseudolymphoma. Such difficulties can in part be ascribed to the morphologic changes such lymphomas can undergo over time. The initially small number of B cells that may be seen at first in PCFCL infiltrates may increase in number in longer-standing lesions. It is also important to recognize that inability to verify monoclonality should not exclude the diagnosis of lymphoma.

Improving live attenuated bacterial carriers for vaccination and therapy.

Live attenuated bacteria are well established as vaccines. Thus, their use as carriers for prophylactic and therapeutic macromolecules is a logical consequence. Here we describe several experimental applications of bacteria to carry heterologous macromolecules into the murine host. First, Listeria monocytogenes are described that are able to transfer eukaryotic expression plasmids into host cells for gene therapy. High multiplicities of infection are still required for efficient gene transfer and we point out some of the bottlenecks that counteract a more efficient transfer and application in vivo. Then, we describe Salmonella enterica serovar Typhimurium (S. typhimurium) as an expression plasmid transfer vehicle for oral DNA vaccination of mice. We demonstrate that the stabilization of the plasmid transformants results in an improved immune response. Stabilization was achieved by replacing the origin of replication of the original high-copy-number plasmid by a low-copy-number origin. Finally, we describe Salmonella carriers for the improved expression of heterologous proteins. We introduce a system in which the plasmid is carried as a single copy during cultivation but is amplified several fold upon infection of the host. Using the same in vivo inducible promoter for both protein expression and plasmid amplification, a substantial increase in antigen expression in vivo can be achieved. A modification of this approach is the introduction of inducible gene expression in vivo with a low-molecular-weight compound. Using P(BAD) promoter and L-arabinose as inducer we were able to deliberately activate genes in the bacterial carrier. No background activity could be observed with P(BAD) such that an inducible suicide gene could be introduced. This is adding an important safety feature to such live attenuated carrier bacteria.

CD8(+) T cells armed with retrovirally transduced IFN-gamma.

Interferon-gamma (IFN-gamma) is considered a key cytokine involved in the preventive and defensive responses of T cells against infectious pathogens and tumors. Therefore, the transgenic expression of IFN-gamma in specific T cells appears to be an obvious therapeutic possibility. To directly examine whether IFN-gamma production can be increased in T cells, we introduced an IFN-gamma encoding cDNA into IFN-gamma(-/-) and IFN-gamma(+/+) CD8(+) effector populations by retroviral transduction. Here, we show that CD8 T cells can be equipped with IFN-gamma that increases their capacity to secrete the cytokine. Despite constitutive retroviral IFN-gamma mRNA transcription, translation and secretion of IFN-gamma protein was tightly regulated and only observed in activated T cells. Neither proliferation nor cytolytic activity of CTL was affected by IFN-gamma transduction. Importantly, CD8(+) T cells retrovirally transduced with IFN-gamma exhibit augmented tumor suppressive capacity upon adoptive transfer into IFN-gamma(-/-) mice. Thus, T cells can be readily armed with IFN-gamma without risking immunopathology by dysregulated production of this highly potent proinflammatory cytokine.

The novel human platelet septin SEPT8 is an interaction partner of SEPT4.

Septins are a family of GTP-binding proteins, which are essential for active membrane movement such as cytokinesis and vesicle trafficking. In non-dividing cells (such as platelets and neurons) septins are implicated in exocytosis. Platelets from a SEPT5 knockout mouse showed an altered serotonin secretion and platelet aggregation, suggesting that SEPT5 is involved in secretion in platelets. Septins form complexes consisting of multiple septin polypeptides. Using the yeast two-hybrid system we had demonstrated that SEPT5 partners with SEPT8. The aim of this study was to identify other interaction partners of the human platelet septin SEPT8. Using the yeast two-hybrid system with SEPT8 as bait protein we identified the human septin SEPT4 as an interaction partner of SEPT8. The interaction between SEPT4 and SEPT8 was confirmed by immunoprecipitation. Expression analysis revealed that SEPT4 is also expressed in human platelets. Thus, SEPT4 is the third described platelet septin besides SEPT5 and SEPT8. Transmission electron microscopy of platelets revealed that SEPT8 and SEPT4 are localized surrounding alpha-granules (as it had been shown for the septin SEPT5) suggesting that the three septins may be components of the septin complex in platelets and contribute in such a way to platelet biology. Activation of platelets by agonists resulted in the translocation of SEPT4 and SEPT8 to the platelet surface indicating a possible functional role of these proteins in platelet granular secretion.

Erythema multiforme-like drug eruption with oral involvement after intake of leflunomide.

Leflunomide is an antirheumatic agent of the type of a 'disease-modifying antirheumatic drug'. In rare cases, severe skin reactions up to the extreme expression of toxic epidermal necrolysis have been observed. A female patient with rheumatoid arthritis had been treated with systemic steroids and methotrexate for 2 years. Five weeks prior to admission to our hospital methotrexate was replaced by leflunomide. Three weeks after initiation of leflunomide therapy a progressive generalized erythema with blistering formation occurred accompanied by increase of body temperature, chills and erosive lesions on the lips and oral mucosa. The palmar and plantar surfaces revealed edema, erythema and pulpitis with epidermolysis. On histologic examination necrotic keratinocytes and epidermal spongiosis were observed. After administration of high-dose prednisolone and topical treatment the patient recovered within 14 days. This is one of the few cases of severe drug reaction after intake of leflunomide. Therefore, the indication of this relatively new drug should be considered carefully.

Diagnostic odyssey of a cutaneous mycobacteriosis rare in central Europe.

Cutaneous infection with Mycobacterium chelonae is an uncommon disease, although this atypical mycobacterium is an acid-fast bacillus ubiquitous in the environment. It is often misdiagnosed and treated as a fungal or common bacterial infection. We report a case of disseminated atypical mycobacterial skin infection of a 72-year-old woman who was treated with different topical and systemic antimycotic and antibiotic drugs over a period of 5 months without remarkable improvement. Eventually, repeated tissue cultures on special medium and performance of PCR led to the diagnosis of M. chelonae infection. The patient was treated successfully with oral clarithromycin within 8 weeks. In case of abscessing cutaneous infection, M. chelonae should be considered in the differential diagnosis of prolonged disease when common antibiotics are not effective after 2-4 weeks of treatment.

High-tech and low-tech orthopaedic surgery in Sub-Saharan Africa.

BACKGROUND: Zambia's governmental health system suffers from shortage of surgical supplies and poor management skills for the sparse resources at hand. The situation has been worsened by the dual epidemics of HIV disease and tuberculosis. On the other hand the private medical sector has benefited greatly from less bureaucracy under the goverment of the Movement for Multi-party Democracy. DISCUSSION: The Zambian-Italian Orthopaedic Hospital in Lusaka is a well organized small unit providing free treatment of physically disabled children. The running costs are met from the fees charged for private consultations, supplemented by donations. State of the art surgical techniques are being used for congenital and acquired musculo-skeletal abnormalities. Last year 513 patients were operated upon free of charge and 320 operations were performed on private patients.