Cognitive impairment in gynecologic cancers: a systematic review of current approaches to diagnosis and treatment

Purpose

To review the etiology and assessment of chemotherapy-related cognitive impairment (CRCI). To explore current treatment and prevention strategies for CRCI and propose future research goals in the field of gynecologic oncology.

Methods

Computerized searches in PubMed of cognitive impairment in cancer between 2000 and 2012 were conducted. The inclusion criteria were randomized control trials evaluating treatment of CRCI and search terms 'cognitive function, cognitive impairment, cognitive decline, chemobrain, chemofog, and cancer'.

Results

To date, numerous modalities have been utilized for assessing CRCI in patients undergoing therapy. It has been proposed to move towards web-based assessment modalities as a possible standard. Few studies have aimed to elucidate possible treatment and prevention options for CRCI; even less in the field of gynecologic oncology. Only seven of these studies were subjected to randomized control trials. Only one of these studies looked at treatment in patients with gynecologic cancers.

Conclusions

The etiology of CRCI is multi-factorial. Following from this, there is no consensus on the best way to assess CRCI although objective measures are more reliable. One must extrapolate data from the non-gynecologic cancer literature, even venturing to non-cancer literature, to explore the treatment and prevention of CRCI. The methods found in these areas of research have not yet been applied to CRCI in gynecologic oncology.     

Stigma in the media: Investigating journalism students attitudes towards mental illness

Given the profound role that media play in public opinion, there exists an ongoing necessity to understand the portrayal of mental illness by journalists. There is a plethora of studies that have examined how mental illness is portrayed in the media, but few studies have sought to understand what journalist opinions about mental illness are, and none could be found regarding journalism students’ opinions. This study aimed to bridge this gap by examining journalism student’s attitudes towards mental illness using the Social Distance Scale (SDS). This study adheres to STROBE guidelines for cross-sectional studies. One hundred and seventy-two undergraduate journalism students (n = 172) completed the SDS with findings suggesting that students had moderate stigmatizing attitudes, with varying degrees of stigma present depending on the social context. Positively framed reporting and constructive media coverage surrounding mental illness may be improved by shared communication and education with health professionals who specialize in mental health: mental health nurses.     

Evaluation of Inflammatory Response to Acute Ischemia Using Near-Infrared Fluorescent Reactive Oxygen Sensors

Purpose

Ischemia-related processes associated with the generation of inflammatory molecules such as reactive oxygen species (ROS) are difficult to detect at the acute stage before the physiologic and anatomic evidence of tissue damage is present. Evaluation of the inflammatory and healing response early after an ischemic event in vivo will aid in treatment selection and patient outcomes. We introduce a novel near-infrared hydrocyanine molecular probe for the detection of ROS as a marker of tissue response to ischemia and a precursor to angiogenesis and remodeling. The synthesized molecular probe, initially a non-fluorescent hydrocyanine conjugated to polyethylene glycol, converts to a highly fluorescent cyanine reporter upon oxidation.

Procedures

The probe was applied in a preclinical mouse model for myocardial infarction, where ligation and removal of a portion of the femoral artery in the hindlimb resulted in temporary ischemia followed by angiogenesis and healing.

Results

The observed increase in fluorescence intensity was approximately sixfold over 24 h in the ischemic tissue relative to the uninjured control limb and was attributed to the higher concentration of ROS in the ischemic tissue.

Conclusions

These results demonstrate the potential for non-invasive sensing for interrogating the inflammatory and healing response in ischemic tissue.     

Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques

In 2012, a novel betacoronavirus, designated Middle East respiratory syndrome coronavirus or MERS-CoV and associated with severe respiratory disease in humans, emerged in the Arabian Peninsula. To date, 108 human cases have been reported, including cases of human-to-human transmission. The availability of an animal disease model is essential for understanding pathogenesis and developing effective countermeasures. Upon a combination of intratracheal, ocular, oral, and intranasal inoculation with 7 × 10⁶ 50% tissue culture infectious dose of the MERS-CoV isolate HCoV-EMC/2012, rhesus macaques developed a transient lower respiratory tract infection. Clinical signs, virus shedding, virus replication in respiratory tissues, gene expression, and cytokine and chemokine profiles peaked early in infection and decreased over time. MERS-CoV caused a multifocal, mild to marked interstitial pneumonia, with virus replication occurring mainly in alveolar pneumocytes. This tropism of MERS-CoV for the lower respiratory tract may explain the severity of the disease observed in humans and the, up to now, limited human-to-human transmission.In June of 2012, a novel betacoronavirus, associated with severe respiratory disease in humans emerged in the Middle East (1, 2), which is closely related to betacoronaviruses circulating in bats (3, 4). The first isolate of Middle East respiratory coronavirus (MERS-CoV) (5), HCoV-EMC/2012, was obtained from a patient with a fatal pneumonia and acute renal failure. To date, 107 additional human cases have been identified, of which 49 were fatal (6). Aside from cases in Saudi Arabia, Qatar, Jordan, and the United Arab Emirates, imported cases have been identified in the United Kingdom, Germany, France, Tunisia, and Italy (6). Although no information is available on the source or route of primary transmission of MERS-CoV, human-to-human transmission has been recorded (7–9). Clinical data on human cases of MERS-CoV infection are currently sparse, but it appears that this virus mainly causes severe lower respiratory tract disease, occasionally accompanied by renal disease. The severity of disease distinguishes MERS-CoV from other coronaviruses circulating in the human population, HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, which are generally associated with upper respiratory tract infections. Instead, MERS-CoV appears to be more similar to the severe respiratory disease caused by severe acute respiratory syndrome (SARS)-CoV.In vitro studies have shown that MERS-CoV replicates efficiently in nonciliated cells in the primary human airway epithelium (10), and in ex vivo human lung cultures MERS-CoV replicated in bronchial, bronchiolar, and alveolar epithelial cells (11), in line with the observed respiratory disease in humans. The recently defined receptor for MERS-CoV, dipeptidylpeptidase 4 (DPP4), is generally expressed in endothelial and epithelial cells and has been shown to be present on cultured human nonciliated bronchiolar epithelium cells (12), providing further information on the respiratory tropism of MERS-CoV.Animal models that recapitulate human disease are essential for understanding pathologic processes involved in disease progression. Moreover, these models are instrumental for the development of prophylactic and therapeutic countermeasures. We have previously shown that rhesus macaques inoculated with a high dose of MERS-CoV isolate HCoV-EMC/2012 developed a respiratory disease reminiscent of that observed in humans (13). To increase our understanding of the pathogenesis of MERS-CoV in the absence of clinical and pathological data from human patients, we present herein a more detailed analysis of the extent of virus replication, the histopathological changes in the respiratory tract and changes in systemic (peripheral blood mononuclear cell, PBMC) and local (lung tissue) gene expression of MERS-CoV–infected rhesus macaques.     

Photochemical Inactivation of Chikungunya Virus in Human Apheresis Platelet Components by Amotosalen and UVA Light

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that recently re-emerged in Africa and rapidly spread into countries of the Indian Ocean basin and South-East Asia. The mean viremic blood donation risk for CHIKV on La Réunion reached 1.5% at the height of the 2005–2006 outbreaks, highlighting the need for development of safety measures to prevent transfusion-transmitted infections. We describe successful inactivation of CHIKV in human platelets and plasma using photochemical treatment with amotosalen and long wavelength UVA illumination. Platelet components in additive solution and plasma units were inoculated with two different strains of high titer CHIKV stock (6.0–8.0 logs/mL), and then treated with amotosalen and exposure to 1.0–3.0 J/cm² UVA. Based on in vitro assays of infectious virus pre- and post-treatment to identify endpoint dilutions where virus was not detectable, mean viral titers could effectively be reduced by > 6.4 ± 0.6 log₁₀ TCID₅₀/mL in platelets and ≥ 7.6 ± 1.4 logs in plasma, indicating this treatment has the capacity to prevent CHIKV transmission in human blood components collected from infected donors in or traveling from areas of CHIKV transmission.     

Room Temperature Ferromagnetic,Anisotropic, Germanium Rich FeGe(001) Alloys

Ferromagnetic Fe_xGe_1−x with x = 2%–9% are obtained by Fe deposition onto Ge(001) at high temperatures (500 °C). Low energy electron diffraction (LEED) investigation evidenced the preservation of the (1 × 1) surface structure of Ge(001) with Fe deposition. X-ray photoelectron spectroscopy (XPS) at Ge 3d and Fe 2p core levels evidenced strong Fe diffusion into the Ge substrate and formation of Ge-rich compounds, from FeGe₃ to approximately FeGe₂, depending on the amount of Fe deposited. Room temperature magneto-optical Kerr effect (MOKE) evidenced ferromagnetic ordering at room temperature, with about 0.1 Bohr magnetons per Fe atom, and also a clear uniaxial magnetic anisotropy with the in-plane [110] easy magnetization axis. This compound is a good candidate for promising applications in the field of semiconductor spintronics.