Defining a new model of interdisciplinary cancer cachexia care in regional Victoria, Australia.

PURPOSE: Cachexia is a wasting condition affecting approximately 50% of cancer patients, associated with decreased quality of life and survival. Barwon Health's Cachexia and Nutrition Support Service provides person-centred interdisciplinary care to assist the management of cachexia symptoms. This study describes a novel and effective service model established in a regional cachexia clinic and the patient population it serves. METHODS: A descriptive, retrospective longitudinal study was conducted of records from patients attending Barwon Health between 2008 and 2013 (n = 175), alongside the description of service refinement over this time. Patients with ≥ 2 attendance dates were assessed for anthropometric measures, follow-up intervals, and muscle function outcomes to describe patient trajectory during clinic involvement. RESULTS: This is the first detailed description of a successful interdisciplinary clinic specific to cancer cachexia management, where patients are seen outside established 8- to 12-week structured programs which prevail in other cachexia clinics. Seventy-five patients (43%) attended one appointment only, with almost half of these (n = 33) first attending within 60 days of death. Of the 99 patients with two or more appointments, 49% displayed positive outcomes with > 2-kg weight gain between two consecutive appointments, and > 50% improved functional strength between two consecutive appointments. CONCLUSIONS: The majority of patients attending clinic multiple times maintained or increased weight and functional status during their involvement with the service. However, successes of care provision were muted by high attrition, primarily due to delayed referral and expected high mortality within the study cohort. Planned future analyses with greater patient numbers and cancer stratification will establish cachectic populations most likely to benefit from this novel mode of interdisciplinary care. The Cachexia and Nutrition Support Service provides an effective and efficient service model for the provision of specialist cachexia care to community-dwelling patients in regional Australia.

Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission.

To gain insight into female-to-male HIV sexual transmission and how male circumcision protects against this mode of transmission, we visualized HIV-1 interactions with foreskin and penile tissues in ex vivo tissue culture and in vivo rhesus macaque models utilizing epifluorescent microscopy. 12 foreskin and 14 cadaveric penile specimens were cultured with R5-tropic photoactivatable (PA)-GFP HIV-1 for 4 or 24 hours. Tissue cryosections were immunofluorescently imaged for epithelial and immune cell markers. Images were analyzed for total virions, proportion of penetrators, depth of virion penetration, as well as immune cell counts and depths in the tissue. We visualized individual PA virions breaching penile epithelial surfaces in the explant and macaque model. Using kernel density estimated probabilities of localizing a virion or immune cell at certain tissue depths revealed that interactions between virions and cells were more likely to occur in the inner foreskin or glans penis (from local or cadaveric donors, respectively). Using statistical models to account for repeated measures and zero-inflated datasets, we found no difference in total virions visualized at 4 hours between inner and outer foreskins from local donors. At 24 hours, there were more virions in inner as compared to outer foreskin (0.0495 +/- 0.0154 and 0.0171 +/- 0.0038 virions/image, p = 0.001). In the cadaveric specimens, we observed more virions in inner foreskin (0.0507 +/- 0.0079 virions/image) than glans tissue (0.0167 +/- 0.0033 virions/image, p<0.001), but a greater proportion was seen penetrating uncircumcised glans tissue (0.0458 +/- 0.0188 vs. 0.0151 +/- 0.0100 virions/image, p = 0.099) and to significantly greater mean depths (29.162 +/- 3.908 vs. 12.466 +/- 2.985 µm). Our in vivo macaque model confirmed that virions can breach penile squamous epithelia in a living model. In summary, these results suggest that the inner foreskin and glans epithelia may be important sites for HIV transmission in uncircumcised men.

Potential HIV-1 target cells in the human penis.

OBJECTIVES: To study the distribution of HIV-1 receptors and degree of keratinization in the human penis. DESIGN: Formalin-fixed penises were obtained from nine uncircumcised cadavers. Foreskins were obtained from 21 healthy adult men undergoing elective circumcision for social reasons. Uncircumcised penises were obtained within 24 h of death from eight men. All tissues were stained for keratin and HIV-1 receptors. METHODS: Penises from nine formalin fixed cadavers aged 64-80 years were obtained from the Department of Anatomy, University of Melbourne. Foreskins were obtained from 21 men aged 18-64 years following circumcision performed at either the Freemason's or Mercy Private Hospitals, Melbourne, Australia. Fresh penile necropsy specimens from eight uncircumcised men aged 23-63 years were obtained from the Victorian Institute of Forensic Medicine, Melbourne. The degree of keratinization was scored, and the distribution of HIV-1 susceptible cells was mapped in the glans penis, penile urethra, urethral meatus, frenulum and foreskin. RESULTS: Cells with HIV-1 receptors were present in all penile epithelia, but Langerhans' cells were most superficial in the inner foreskin and frenulum. The inner foreskin had a significantly thinner keratin layer (1.8 +/- 0.1 units), than the outer foreskin (3.3 +/- 0.1), or glans penis (3.3 +/- 0.2), P < 0.05. CONCLUSIONS: Superficial Langerhans' cells on the inner aspect of the foreskin and frenulum are poorly protected by keratin and thus could play an important role in primary male infection. These findings provide a possible anatomical explanation for the epidemiologically observed protective effect of male circumcision.

Short-chain fatty acids increase expression and secretion of stromal cell-derived factor-1 in mouse and human pre-adipocytes.

OBJECTIVE: Stromal cell-derived factor-1 (SDF-1) is expressed in pre-adipocytes but its role is unknown. We investigated butyrate (a histone deacetylase inhibitor--HDACi) and other short-chain fatty acids (SCFA) in the regulation of SDF-1. We further investigated whether effects of SCFA were signalled through G protein-coupled receptors FFA2 and FFA3. DESIGN AND RESULTS: SDF-1 mRNA expression and protein secretion were studied in 3T3-L1 cells and human pre-adipocytes. SDF-1 was abundant, with mRNA and protein levels increased by butyrate. This was replicated with acetate and propionate, but not with trichostatin or valproate. Trichostatin inhibited SDF-1 secretion. Pertussis toxin blocked stimulation by butyrate. The order of potency of SCFA in stimulating SDF-1 (C3 > C4 > C2) is consistent with action through FFA3. Silencing the FFA3 gene abolished butyrate-stimulated SDF-1 expression and secretion. FFA3 was expressed in both pre-adipocytes and adipocytes, while FFA2 was expressed in adipocytes only. SDF-1 expression was low in murine macrophage J774.2 cells, while the SDF-1 receptor CXCR4 was absent from 3T3-L1 cells but abundant in J774.2 macrophages. In human pre-adipocytes, FFA3 was also expressed and SCFA increased SDF-1 secretion. CONCLUSIONS: SDF-1 and CXCR4 may mediate the interaction between adipose stromal cells and macrophages. Effects of SCFA are mediated through FFA3, but not histone deacetylase inhibition.

Sperm immobilizing properties of lemon juice.

The aim of this study was to evaluate the sperm-immobilizing properties of lemon juice to determine if they are consistent with its traditional contraceptive use. It was found that lemon juice supernatant (LJS) has high osmolality (550-60 mOsm) and low pH (2.2-2.6) and that addition of LJS to semen to give a final concentration of 20% v/v reduced the pH from around 8.4 to 4.1. This acidification was associated with irreversible cessation of all sperm movements within 1 minute. In conclusion, lemon juice should be further evaluated for acceptability, safety, and efficacy as a topical vaginal contraceptive agent.