An evolutionary perspective on human female sexual desire

The maternal mortality rate in the Third World remains high despite the launch of the Safe Motherhood Initiative (SMI) in 1987. There are various sociocultural, political and economic factors which play a major role in this. The five main causes of maternal mortality are haemorrhage, sepsis, unsafe abortion, hypertensive disorders and obstructed labour. The key to safe motherhood lies in providing quality maternity care for all women. It is important to know the nature and the extent of the problems in the community so that appropriate technology can be introduced with optimum utilization of the available resources. The different ways of achieving safe motherhood are discussed with emphasis on community based interventions. The SMI goals can be reached provided the Safe Motherhood programmes are well funded, the community workers well trained and the leaders of the community and the nation dedicated.     

AMIGO2 mRNA expression in hippocampal CA2 and CA3a

AMIGO2, or amphoterin-induced gene and ORF (open reading frame) 2, belongs to the leucine-rich repeats and immunoglobulin superfamilies. The protein is a downstream target of calcium-dependent survival signals and, therefore, promotes neuronal survival. Here, we describe the mRNA distribution pattern of AMIGO2 throughout the mouse brain with special emphasis on the hippocampus. In the Ammon’s horn, a detailed comparison between the subregional mRNA expression patterns of AMIGO2 and Pcp4 (Purkinje cell protein 4)—a known molecular marker of hippocampal CA2 (Cornu Ammonis 2)—revealed a prominent AMIGO2 mRNA expression level in both the CA2 and the CA3a (Cornu Ammonis 3a) subregion of the dorsal and ventral hippocampus. Since this CA2/CA3a region is particularly resistant to neuronal injury and neurotoxicity [Stanfield and Cowan (Brain Res 309(2):299–307 1984); Sloviter (J Comp Neurol 280(2):183–196 1989); Leranth and Ribak (Exp Brain Res 85(1):129–136 1991); Young and Dragunow (Exp Neurol 133(2):125–137 1995); Ochiishi et al. (Neurosci 93(3):955–967 1999)], we suggest that the expression pattern of AMIGO2 indeed fits with its involvement in neuroprotection.     

Systemic CD4+ and CD8+ T-cell cytokine profiles correlate with GOLD stage in stable COPD

Chronic obstructive pulmonary disease (COPD) is associated with pulmonary and systemic inflammation. Both CD4+ and CD8+ T-lymphocytes play a key role in COPD pathogenesis, but cytokine profiles in circulating T-lymphocytes have not been well characterised. Here we report the analysis of peripheral blood T-cells from 30 stable COPD patients and 10 healthy never-smokers for interferon (IFN)-γ, interleukin (IL)-4, tumour necrosis factor (TNF)-α and the T-helper 17 cytokines IL-17A, IL-17F and IL-22 by intracellular flow cytometry. We found significantly increased proportions of IFN-γ+ and TNF-α+ CD8+ T-cells in COPD patients, when compared with healthy controls. This was most evident in patients with less severe disease. In contrast, expression profiles in circulating CD4+ T-cells were similar in COPD patients and healthy controls for all cytokines tested, except for IL-17F. COPD patients with more severely reduced diffusing capacity had lower proportions of IL-17A+ CD4+ T-cells. Proportions of IL-22+ cells in the CD4+ memory T-cell population were significantly increased in active smokers, when compared with past smokers. Collectively, this comprehensive cytokine analysis of circulating T-cells in COPD patients revealed a correlation for CD8+ T-cells between Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and IFN-γ or TNF-α expression, but not for CD4+ T-cells.     

The maintenance gap: a new theoretical perspective on the evolution of aging

One of the prevailing theories of aging, the disposable soma theory, views aging as the result of the accumulation of damage through imperfect maintenance. Aging, then, is explained from an evolutionary perspective by asserting that this lack of maintenance exists because the required resources are better invested in reproduction. However, the amount of maintenance necessary to prevent aging, 'maintenance requirement' has so far been largely neglected and has certainly not been considered from an evolutionary perspective. To our knowledge we are the first to do so, and arrive at the conclusion that all maintenance requirement needs an evolutionary explanation. Increases in maintenance requirement can only be selected for if these are linked with either higher fecundity or better capabilities to cope with environmental challenges to the integrity of the organism. Several observations are suggestive of the latter kind of trade-off, the existence of which leads to the inevitable conclusion that the level of maintenance requirement is in principle unbound. Even the allocation of all available resources to maintenance could be unable to stop aging in some organisms. This has major implications for our understanding of the aging process on both the evolutionary and the mechanistic level. It means that the expected effect of measures to reallocate resources to maintenance from reproduction may be small in some species. We need to have an idea of how much maintenance is necessary in the first place. Our explorations of how natural selection is expected to act on the maintenance requirement provides the first step in understanding this.     

Antibiotics produced by Streptomyces

Streptomyces is a genus of Gram-positive bacteria that grows in various environments, and its shape resembles filamentous fungi. The morphological differentiation of Streptomyces involves the formation of a layer of hyphae that can differentiate into a chain of spores. The most interesting property of Streptomyces is the ability to produce bioactive secondary metabolites, such as antifungals, antivirals, antitumorals, anti-hypertensives, immunosuppressants, and especially antibiotics. The production of most antibiotics is species specific, and these secondary metabolites are important for Streptomyces species in order to compete with other microorganisms that come in contact, even within the same genre. Despite the success of the discovery of antibiotics, and advances in the techniques of their production, infectious diseases still remain the second leading cause of death worldwide, and bacterial infections cause approximately 17 million deaths annually, affecting mainly children and the elderly. Self-medication and overuse of antibiotics is another important factor that contributes to resistance, reducing the lifetime of the antibiotic, thus causing the constant need for research and development of new antibiotics.     

Impact of total PSA, PSA doubling time and PSA velocity on detection rates of 11C-Choline positron emission tomography in recurrent prostate cancer

Purpose

To evaluate the effect of total PSA (tPSA) and PSA kinetics on the detection rates of ¹¹C-Choline PET in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) or external beam radiotherapy (EBRT).

Methods

We included 185 patients with BCR after RP (PSA >0.2 ng/ml) or after EBRT (ASTRO definition). After injection of 400 MBq ¹¹C-Choline i.v., a scan was made using the ECAT HR + PET camera with CT fusion images or Siemens mCT PET/CT. Biopsy-proven histology, confirmative imaging (CT or bone scan) and/or clinical follow-up (PSA) were used as composite reference. Statistical analysis was performed using PASW Statistics 18.

Results

¹¹C-Choline PET was positive in 124/185 cases (65 %) (in 22/61 (36 %) after RP, 102/124 (82 %) after EBRT). In 79 patients a local recurrence was identified, and 45 patients showed locoregional metastases on PET/CT. In 20 cases a proven false-negative PET scan was observed. Positive PET scans were confirmed by histology in 87/124 (70 %) cases, by confirmatory imaging in 34/124 (28 %) and by clinical follow-up after salvage treatment in 3 (2 %) cases. The ROC analysis to detect a recurrence showed significant difference in area under the curve (AUC) of tPSA 0.721(p < 0.001) and PSA velocity 0.730 (p < 0.001). PSA doubling time showed no significant difference with an AUC of 0.542 (p = 0.354). Detection rates are <50 % in tPSA <2 ng/ml and/or PSA velocity <1 ng/ml/year.

Conclusions

Total serum PSA and PSA velocity have significant effect on the detection rates of ¹¹C-Choline PET/CT in men with a BCR after RP or EBRT.     

Patterns of Care in the Administration of Neo‐adjuvant Chemotherapy for Breast Cancer. A Population‐Based Study

Neo‐adjuvant chemotherapy (NAC) is used to facilitate radical surgery for initially irresectable or locally advanced breast cancer. The indication for NAC has been extended to clinically node negative (cN0) patients in whom adjuvant systemic therapy is foreseen. A population‐based study was conducted to evaluate the increasing use of NAC, breast conserving surgery (BCS) after NAC and timing of the sentinel node biopsy (SNB). All female breast cancer patients, treated in 10 hospitals in the Eindhoven Cancer Registry area in the Netherlands between January 2003 and June 2012 were included (N = 18,427). In total, 1,402 patients (7.6%) received NAC. The administration increased from 2.5% in 2003 to 13.0% in 2011 (p < 0.001). Use of NAC increased from 0.5% to 2.3% for cT1 tumors, from 2.8% to 27.0% for cT2, from 30.6% to 70.9% for cT3, and from 40.5% to 58.1% for cT4 tumors (p < 0.001). In cN0 patients, use of NAC increased from 1.0% to 4.4% and in clinically node positive patients from 12.0% to 57.5% (p < 0.001). Downsizing of the tumor and BCS are achieved increasingly. In 2011, in three hospitals NAC was administered in <10% of patients, in five hospitals in 10–15% and in two hospitals the proportion of patients receiving NAC was >20% (p < 0.001). Of the 1,402 patients with NAC, 495 patients underwent SNB, 91.5% of whom prior to NAC. In the Netherlands up to one in eight patients receive NAC. The administration of NAC and the percentage of BCS increased over the past decade, especially in cT2 tumors. Considerable hospital variation in the administration of NAC exists.