Depression and sexual dysfunction are both common in the general population. When they co-exist they have the potential to impact negatively on each other in a bidirectional manner. Medication used to treat depression may cause additional problems with the sexual response cycle; although no drug is completely innocent, serotonergic agents such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) are most frequently implicated in antidepressant-induced sexual dysfunction. Adherence to long-term treatment may be compromised, which may have serious consequences. Various psychological and pharmacological strategies, including the ad hoc use of sildenafil, may offer some respite.

BackgroundHuman epidermal growth factor receptor-2 (Her-2) is over expressed in approximately 25-30% of all primary breast tumors resulting in a distinctive breast cancer subtype associated with a poor prognosis and a decrease in overall survival. Trastuzumab (Herceptin®), an anti-Her-2 monoclonal antibody, has dramatically altered the prognosis of Her-2 positive breast cancer. Trastuzumab is, however, associated with primary and acquired resistance.Aim and methodsTo investigate the in-vitro effects of trastuzumab on cell viability (tetrazolium conversion assay), cell cycling (propidium iodide staining), apoptosis (executioner caspases and annexin-V) and relative surface Her-2 receptor expression (anti-Her-2 affibody molecule) in Her-2-positive (SK-Br-3) and oestrogen receptor positive (MCF-7) breast adenocarcinoma cells and to determine potential augmentation of these effects by two endogenous ligands, epidermal growth factor (EGF) and heregulin-β1 (HRG- β1).ResultsCell viability was decreased in SK-Br-3 cells by exposure to trastuzumab. This was associated with G1 accumulation and decreased relative surface Her-2 receptor density, supporting the cytostatic nature of trastuzumab in vitro. SK-Br-3 cells exposed to EGF and heregulin-β1 produced differential cell responses alone and in combination with trastuzumab, in some instances augmenting cell viability and cell cycling. Relative surface Her-2 receptor density was reduced substantially by trastuzumab, EGF and heregulin-β1. These reductions were amplified when ligands were used in combination with trastuzumab.ConclusionCell type specific interactions of endogenous ligands appear to be dependent on absolute Her-receptor expression and cross activation of signaling pathways. This supports the notion that receptor density of Her-family members and multiplicity of growth ligands are of mutual importance in breast cancer cell proliferation and therefore also in resistance associated with trastuzumab.

COVID-19 patients may face a long and winding road to recovery. Outcomes of critically ill patients have been well described, including in China, Italy and the USA, and particularly in the comorbid elderly. However, short-, medium- and long-term health consequences are being realised not only in those that were hospitalised, but also in outpatients with milder or asymptomatic illness.

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At some point in their career, at least a third of doctors suffer personal health problems such as injury, aging, or physical and mental illness, which detract from their ability to function properly and to practice medicine safely. In most, impairment is amenable to intervention, treatment, recovery or resolution. However, some conditions, notably depression, may be overrepresented in the medical profession, under-recognized, stigmatised and undertreated, which may have fatal consequences.