Oxidative stress-dependent MMP-13 activity underlies glucose neurotoxicity

Background

A complication of diabetes is neuropathy, a condition of sensory axon degeneration that originates in the epidermis. The mechanisms remain unknown but reactive oxygen species (ROS) have been implicated in this condition. In this study, we assessed the role of ROS and a candidate downstream target, MMP-13 in glucose-induced sensory axon degeneration in zebrafish and mice.

Exacerbation of pulmonary lymphangioleiomyomatosis by exogenous estrogens

A 48-year-old woman with profound, rapidly progressive dyspnea requested a second opinion regarding the diagnosis and management of an undiagnosed interstitial process. One year prior to this evaluation, she had been placed on therapy with exogenous estrogens for the treatment of osteoporosis. During this therapy, she had a marked deterioration of her pulmonary status. Review of her open lung biopsy, which was obtained five years previously, revealed lymphangioleiomyomatosis. Discontinuation of estrogen therapy and treatment with tamoxifen were successful in stopping the progressive course. This patient's clinical course suggested an association between estrogen therapy and clinical deterioration during the menopause.     

Effectiveness of methyl-GAG (methylglyoxal-bis[guanylhydrazone]) in patients with advanced malignant lymphoma

We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl- GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma.     

Human Mate Selection and Addiction: a Conceptual Critique

The authors review past work on modeling human mate selection, and suggest, using illustrations from existing literature on the impact of alcoholism on relationship formation and dissolution and reproduction, that the challenges of adequately characterizing human mate selection have not yet been overcome. Some paths forwards are suggested.     

Comparing monitoring and production based approaches to the treatment of phonological assembly difficulties in aphasia

Background: Waldron, Whitworth, and Howard (2011 Waldron, H., Whitworth, A. and Howard, D. 2011. Therapy for phonological assembly difficulties: A case series. Aphasiology, 25(4): 434–455. [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]) replicated the auditory and monitoring therapy reported in a single case by Franklin, Buerk, and Howard (2002 Franklin, S., Buerk, F. and Howard, D. 2002. Generalised improvement in speech production for a subject with reproduction conduction aphasia. Aphasiology, 16(10/11): 1087–1114. [Taylor & Francis Online] , [Google Scholar]) with four participants with phonological assembly difficulties. No participant responded in the same way as Franklin et al.’s client MB and, notably, all improvements seen were item-specific, in contrast to MB who had shown generalised improvements in naming, repetition, and reading aloud. Waldron et al. attributed this difference to the combination of underlying impairments in their participants, in particular additional lexical deficits; it remains unknown whether Franklin et al.’s results would be replicated in someone with a more pure phonological assembly difficulty. It is also unknown whether a more direct therapy approach, targeting a reduction in the production of phonological errors, rather than improving monitoring, might also be effective with this client group.

Aims: The current study aimed to compare the effectiveness of the auditory and monitoring therapy reported by Franklin et al. (2002 Franklin, S., Buerk, F. and Howard, D. 2002. Generalised improvement in speech production for a subject with reproduction conduction aphasia. Aphasiology, 16(10/11): 1087–1114. [Taylor & Francis Online] , [Google Scholar]) with a production-focused therapy based on the articulatory kinematic treatment of apraxia of speech (AOS), in a single participant with phonological assembly difficulties.

Methods & Procedures: Participant RE received three consecutive therapy phases: Franklin et al.’s auditory therapy, followed by a new production therapy involving a hierarchy of articulatory kinematic cues and the production of minimal contrast pairs, and finally Franklin et al.’s monitoring therapy. As RE's linguistic profile was similar to that of Franklin et al.’s client, it was predicted that he would make similar gains, i.e., generalised improvement in the production of treated and untreated words, following all three therapy types.

Outcomes & Results: RE's naming of treated items improved significantly after both the production therapy and the monitoring therapy, but naming of untreated items did not improve and there were no naming improvements following the auditory therapy.

Conclusions: Two possible reasons why RE did not respond as predicted are discussed. First, that RE may have had additional lexical retrieval difficulties, in which case therapy could have improved the link between semantics and lexical phonology; and second, that RE may have had additional mild AOS, in which case therapy may have resulted in improved motor planning abilities. Neither of these hypotheses could fully account for all of RE's results. Nonetheless, the production therapy was shown to be an effective alternative approach for clients with phonological assembly difficulties, when a direct focus on speech production is needed.