Cognitive dysfunctions in elderly cancer patients: A new challenge for oncologists

While chemotherapy is more commonly proposed to the elderly population with cancer, little is known about the impact of therapy on cognitive functions and the way of managing such dysfunctions in clinical practice among this population. Aging by itself is associated with cognitive modifications, comorbidities and functional decline, which may have a significant impact on the autonomy. In elderly patients with cancer, several factors like the biologic processes underlying the disease and therapies will contribute to favor the cognitive decline. The chemobrain phenomenon, referring to the chemotherapy-induced impairment of memory, executive function or information processing speed has been extensively described in patients with breast cancer, and the few studies available in older patients suggest that the impact could be more pronounced in patients with pre-existing troubles.     

Experimental Staphylococcus aureus arthritis in mice.

Staphylococcus aureus arthritis is usually caused by bacteremia and is highly destructive. Controlled studies on septic arthritis in humans are difficult to perform, because the time of onset of the infection is unknown. Animal models of bacterial arthritis make it possible to control important variables in experimental studies. We present a mouse model of S. aureus arthritis in which the intravenous administration of 10(7) cells of S. aureus LS-1 induced arthritis or osteitis or both within 3 weeks in 80 to 90% of the mice. Signs of arthritis emerged within the first few days after the injection. An interesting finding was that the S. aureus strain used in this study binds bone sialoprotein, a glycoprotein known to be specifically localized to bone tissue. This new model of S. aureus arthritis enables the study of the kinetics of joint destruction and the host-bacterium relationship as well as therapeutical approaches to septic arthritis and osteomyelitis.     

Huntington's Disease (HD): Neurodegeneration of Brodmann's Primary Visual Area 17 (BA17)

Huntington's disease (HD), an autosomal dominantly inherited polyglutamine or CAG repeat disease along with somatomotor, oculomotor, psychiatric and cognitive symptoms, presents clinically with impairments of elementary and complex visual functions as well as altered visual‐evoked potentials (VEPs). Previous volumetric and pathoanatomical post‐mortem investigations pointed to an involvement of Brodmann's primary visual area 17 (BA17) in HD. Because the involvement of BA17 could be interpreted as an early onset brain neurodegeneration, we further characterized this potential primary cortical site of HD‐related neurodegeneration neuropathologically and performed an unbiased estimation of the absolute nerve cell number in thick gallocyanin‐stained frontoparallel tissue sections through the striate area of seven control individuals and seven HD patients using Cavalieri's principle for volume and the optical disector for nerve and glial cell density estimations. This investigation showed a reduction of the estimated absolute nerve cell number of BA17 in the HD patients (71 044 037 ± 12 740 515 nerve cells) of 32% in comparison with the control individuals (104 075 067 ± 9 424 491 nerve cells) (Mann–Whitney U‐test; P < 0.001). Additional pathoanatomical studies showed that nerve cell loss was most prominent in the outer pyramidal layer III, the inner granular layers IVa and IVc as well as in the multiform layer VI of BA17 of the HD patients. Our neuropathological results in BA17 confirm and extend previous post‐mortem, biochemical and in vivo neuroradiological HD findings and offer suitable explanations for the elementary and complex visual dysfunctions, as well as for the altered VEP observed in HD patients.     

Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials

Background

In women, low sexual desire and/or sexual arousal can lead to sexual dissatisfaction and emotional distress, collectively defined as female sexual interest/arousal disorder (FSIAD). Few pharmaceutical treatment options are currently available.

Leisure time sport activities and maximal aerobic power during late adolescence

Summary The pattern of leisure time sport activity was estimated by retrospective recalls and expressed in terms of an annual sport activity score. The activity score was related to the development of maximal aerobic power during the period of late adolescence in German children. Both girls and boys reduced their activity pattern from 14 to 18 years of age, boys more than girls. At each age boys were more active than girls. A slight tendency towards better fitness with increased habitual physical activity was noticed, but many sedentary children exhibited a good performance capacity and some children with a high level of leisure time sport activity were characterized by a low level of maximal aerobic power. A statistical analysis revealed that the observed tendency to better fitness with increased habitual physical activity could be explained by an age factor with no additional effect of variation in sport activity score.     

Intestinal resistance to cholera toxin in mouse. Antitoxic antibodies and desensitization of adenylate cyclase

Mice were immunized perorally with cholera toxin (CT), cholera B-subunit (CB), or buffer as control. The response of anti-CT antibodies of the IgG, IgA and IgM class in bile, IgA being predominating, were similar in both immunized groups. The same number of anti-CT containing plasma cells (ACC) were determined in the intestinal lamina propria of CT - as well as of CB-immunized mice 20 days after the last immunization, while ACC at day 4 in the CB group were 50% higher than in the CT group. In contrast to the vigorous antibody response to CT in both groups of immunized mice, only animals immunized with CT displayed resistance to CT-induced intestinal hypersecretion and to CT stimulation of adenylate cyclase. The CB-treated group responded to CT with fluid accumulation and enzyme activation similar to controls. The results suggest that intestinal resistance to CT in mouse is due to desensitization of adenylate cyclase rather than to CT-neutralizing antibodies.     

Flibanserin and 8‐OH‐DPAT Implicate Serotonin in Association between Female Marmoset Monkey Sexual Behavior and Changes in Pair‐Bond Quality

IntroductionPsychopathological origins of personally distressing, hypoactive sexual desire disorder (HSDD) in women are unknown, but are generally attributed to an inhibitory neural regulator, serotonin (5‐HT). Flibanserin, a 5‐HT_1A agonist and 5‐HT_2A antagonist, shows promise as a treatment for HSDD.AimTo test the hypothesis that female marmoset sexual behavior is enhanced by flibanserin and diminished by 8‐OH‐DPAT, in order to evaluate the efficacy of serotonergic modulation of female sexual behavior in a pairmate social setting comparable to humans.MethodsSexual and social behavior were examined in eight female marmoset monkeys receiving daily flibanserin (15 mg/kg), 8‐OH‐DPAT (0.1 mg/kg), or corresponding vehicle for 15–16 weeks in a counterbalanced, within‐subject design, while housed in long‐term, stable male–female pairs.Main Outcome MeasuresMarmoset pairmate interactions, including sexual and social behavior, were scored during weeks 5–6 of daily flibanserin, 8‐OH‐DPAT or vehicle treatment. 24‐hour pharmacokinetic profiles of the drugs and their metabolites, as well as drug‐induced acute symptoms of the 5‐HT behavioral syndrome were also assessed.ResultsTwo‐way analysis of variance reveals that flibanserin‐treated females attract more male sexual interest (P = 0.020) and trigger increased grooming (P = 0.001) between partners. In contrast, 8‐OH‐DPAT‐treated females show increased rejection of male sexual advances (P = 0.024), a tendency for decreased male sexual interest (P = 0.080), and increased aggression with their male pairmates (P = 0.049).ConclusionsWhile 8‐OH‐DPAT‐treated female marmosets display decreased sexual receptivity and increased aggressive interactions with their male pairmates, flibanserin‐treated female marmosets demonstrate increased affiliative behavior with their male pairmates. Such pro‐affiliation attributes may underlie flibanserin's effectiveness in treating HSDD in women. Aubert Y, Gustison ML, Gardner LA, Bohl MA, Lange JR, Allers KA, Sommer B, Datson NA, and Abbott DH. Flibanserin and 8‐OH‐DPAT implicate serotonin in association between female marmoset monkey sexual behavior and changes in pair‐bond quality. J Sex Med 2012;9:694–707.     

Clinical and Biopsychosocial Determinants of Sexual Dysfunction in Middle‐Aged and Older Australian Men

IntroductionErectile dysfunction (ED) and other related sexual dysfunctions in men have recently been shown to associate with a range of conditions and biopsychosocial factors. However, few studies have been able to control for these related factors simultaneously.AimTo determine the prevalence of and associated risk factors for ED and low solitary and dyadic sexual desire.Main Outcome MeasuresErectile function (International Index of Erectile Function‐erectile function) and sexual desire (Sexual Desire Inventory 2), as well as associated sociodemographic, lifestyle, biological, and clinical risk factors.MethodsData were collected from 1,195 randomly selected, community‐dwelling men as part of the Florey Adelaide Male Ageing Study.ResultsThe prevalence of ED, low solitary, and dyadic sexual desire was 17.7%, 67.7%, and 13.5%, respectively. Increasing age, abdominal fat mass, obstructive sleep apnea risk, and the absence of a regular partner were associated with both degrees of ED severity. Insufficient physical activity, low alcohol consumption, and hypertension were associated with mild ED only, and voiding lower urinary tract symptoms, diabetes, and lower plasma testosterone were independently associated with moderate to severe ED. Increasing age, lower alcohol consumption, insufficient physical activity, and a diagnosis of depression, anxiety, or insomnia were associated with both low dyadic and solitary sexual desire. Postschool qualifications and lower plasma testosterone were associated with low dyadic desire, whereas lower education and income, unemployment, and migration were associated with low solitary sexual desire. The absence of a regular partner and postschool qualifications were associated with higher solitary sexual desire.ConclusionsWhile ED and low dyadic and solitary sexual desire share some risk factors, we were able to demonstrate that unique factors exist for each of these domains. Attention should first be given to addressing these modifiable risk factors. Martin S, Atlantis E, Wilson D, Lange K, Haren MT, Taylor A, Wittert G, and Members of the Florey Adelaide Male Ageing Study. Clinical and biopsychosocial determinants of sexual dysfunction in middle‐aged and older Australian men. J Sex Med 2012;9:2093–2103.