MHC-correlated odour preferences in humans and the use of oral contraceptives

Previous studies in animals and humans show that genes in the major histocompatibility complex (MHC) influence individual odours and that females often prefer odour of MHC-dissimilar males, perhaps to increase offspring heterozygosity or reduce inbreeding. Women using oral hormonal contraceptives have been reported to have the opposite preference, raising the possibility that oral contraceptives alter female preference towards MHC similarity, with possible fertility costs. Here we test directly whether contraceptive pill use alters odour preferences using a longitudinal design in which women were tested before and after initiating pill use; a control group of non-users were tested with a comparable interval between test sessions. In contrast to some previous studies, there was no significant difference in ratings between odours of MHC-dissimilar and MHC-similar men among women during the follicular cycle phase. However, single women preferred odours of MHC-similar men, while women in relationships preferred odours of MHC-dissimilar men, a result consistent with studies in other species, suggesting that paired females may seek to improve offspring quality through extra-pair partnerships. Across tests, we found a significant preference shift towards MHC similarity associated with pill use, which was not evident in the control group. If odour plays a role in human mate choice, our results suggest that contraceptive pill use could disrupt disassortative mate preferences.     

Scent-marking by male mice under the risk of predation

The use by predators of scent marks made by potential prey isa largely unexplored potential cost of olfactory signaling.Here we investigate how animals that differ in their investmentin scent-marking respond to simulated predation risk, by comparingthe willingness to approach and counter-mark the scent marksof a competitor in the presence or absence of predator odor.We aimed to test whether animals that invest heavily in scent-marking,and which may thus be more vulnerable to eavesdropping predators,will either (1) take greater risks to counter-mark the competitor'sscent or (2) reduce or abandon scent-marking. Using outbredmale laboratory mice, Mus musculus, we show that, in the absenceof predators, individuals which initially scent-mark at highfrequency (high markers) approach the competitor's scent marksmore quickly and spend more time in counter-marking than thosewhich initially invest relatively little (low markers). Ina sib-sib experimental design, simulated presence of predationrisk (urine of ferrets, Mustela putorius furo) caused bothkinds of individual to approach the competitor's marks moreslowly, but high markers approached more quickly than low markersand spent more time in the vicinity of the competitor's marks.Only high markers significantly reduced their overmarking ofthe competitor's scent. These results suggest (1) that thereis a unique danger inherent to scent-marking at high frequenciesand (2) that high-marking males were prepared to accept increasedcosts of intrasexual competition in order to reduce the riskof predation. Further tests using the scent of naked mole-rats, Heterocephalus glaber, showed that these effects were not elicited simply by an unfamiliar odor. We discuss reasons for the observeddifference in response to predation risk between the groups,and the implications of these results for counter-selectionon scent-marking strategies.     

Monocyte chemoattractant protein-1 mediates cockroach allergen-induced bronchial hyperreactivity in normal but not CCR2-/- mice: the role of mast cells.

Bronchial eosinophil and mononuclear cell infiltrates are a hallmark of the asthmatic lung and are associated with the induction of reversible airway hyperreactivity. In these studies, we have found that monocyte chemotactic protein-1 (MCP-1), a CC (beta) chemokine, mediates airway hyperreactivity in normal and allergic mice. Using a murine model of cockroach Ag-induced allergic airway inflammation, we have demonstrated that anti-MCP-1 Abs inhibit changes in airway resistance and attenuate histamine release into the bronchoalveolar lavage, suggesting a role for MCP-1 in mast cell degranulation. In normal mice, instillation of MCP-1 induced prolonged airway hyperreactivity and histamine release. In addition, MCP-1 directly induced pulmonary mast cell degranulation in vitro. These latter effects would appear to be selective because no changes were observed when macrophage-inflammatory protein-1alpha, eotaxin, or MCP-3 were instilled into the airways of normal mice or when mast cells were treated in vitro. Airway hyperreactivity was mediated by MCP-1 through CCR2 because allergen-induced as well as direct MCP-1 instilled-induced changes in airway hyperreactivity were significantly attenuated in CCR2 -/- mice. The neutralization of MCP-1 in allergic animals and instillation of MCP-1 in normal animals was related to leukotriene C4 levels in the bronchoalveolar lavage and was directly induced in pulmonary mast cells by MCP-1. Thus, these data identify MCP-1 and CCR2 as potentially important therapeutic targets for the treatment of hyperreactive airway disease.     

Impact of mental disorders on clinical outcomes of physical diseases: an umbrella review assessing population attributable fraction and generalized impact fraction

Empirical evidence indicates a significant bidirectional association between mental disorders and physical diseases, but the prospective impact of men­tal disorders on clinical outcomes of physical diseases has not been comprehensively outlined. In this PRISMA- and COSMOS-E-compliant umbrella review, we searched PubMed, PsycINFO, Embase, and Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports, up to March 15, 2022, to identify systematic reviews with meta-analysis that examined the prospective association between any mental disorder and clinical outcomes of physical diseases. Primary outcomes were disease-specific mortality and all-cause mortality. Secondary outcomes were disease-specific incidence, functioning and/or disability, symptom severity, quality of life, recurrence or progression, major cardiac events, and treatment-related outcomes. Additional inclusion criteria were further applied to primary studies. Random effect models were employed, along with I² statistic, 95% prediction intervals, small-study effects test, excess significance bias test, and risk of bias (ROBIS) assessment. Associations were classified into five credibility classes of evidence (I to IV and non-significant) according to established criteria, complemented by sensitivity and subgroup analyses to examine the robustness of the main analysis. Statistical analysis was performed using a new package for conducting umbrella reviews ( https://metaumbrella.org ). Population attributable fraction (PAF) and generalized impact fraction (GIF) were then calculated for class I-III associations. Forty-seven systematic reviews with meta-analysis, encompassing 251 non-overlapping primary studies and reporting 74 associations, were included (68% were at low risk of bias at the ROBIS assessment). Altogether, 43 primary outcomes (disease-specific mortality: n=17; all-cause mortality: n=26) and 31 secondary outcomes were investigated. Although 72% of associations were statistically significant (p<0.05), only two showed convincing (class I) evidence: that between depressive disorders and all-cause mortality in patients with heart failure (hazard ratio, HR=1.44, 95% CI: 1.26-1.65), and that between schizophrenia and cardiovascular mortality in patients with cardiovascular diseases (risk ratio, RR=1.54, 95% CI: 1.36-1.75). Six associations showed highly suggestive (class II) evidence: those between depressive disorders and all-cause mortality in patients with diabetes mellitus (HR=2.84, 95% CI: 2.00-4.03) and with kidney failure (HR=1.41, 95% CI: 1.31-1.51); that between depressive disorders and major cardiac events in patients with myocardial infarction (odds ratio, OR=1.52, 95% CI: 1.36-1.70); that between depressive disorders and dementia in patients with diabetes mellitus (HR=2.11, 95% CI: 1.77-2.52); that between alcohol use disorder and decompensated liver cirrhosis in patients with hepatitis C (RR=3.15, 95% CI: 2.87-3.46); and that between schizophrenia and cancer mortality in patients with cancer (standardized mean ratio, SMR=1.74, 95% CI: 1.41-2.15). Sensitivity/subgroup analyses confirmed these results. The largest PAFs were 30.56% (95% CI: 27.67-33.49) for alcohol use disorder and decompensated liver cirrhosis in patients with hepatitis C, 26.81% (95% CI: 16.61-37.67) for depressive disorders and all-cause mortality in patients with diabetes mellitus, 13.68% (95% CI: 9.87-17.58) for depressive disorders and major cardiac events in patients with myocardial infarction, 11.99% (95% CI: 8.29-15.84) for schizophrenia and cardiovascular mortality in patients with cardiovascular diseases, and 11.59% (95% CI: 9.09-14.14) for depressive disorders and all-cause mortality in patients with kidney failure. The GIFs confirmed the preventive capacity of these associations. This umbrella review demonstrates that mental disorders increase the risk of a poor clinical outcome in several physical diseases. Prevention targeting mental disorders – particularly alcohol use disorders, depressive disorders, and schizophrenia – can reduce the incidence of adverse clinical outcomes in people with physical diseases. These findings can inform clinical practice and trans-speciality preventive approaches cutting across psychiatric and somatic medicine.     

Histochemical light microscopic study of catecholamine containing paraganglia in the human pelvis

Summary Histological and histochemical techniques have been employed to determine the structure and autonomic innervation of paraganglia located in the human pelvis. In foetal and early postnatal tissues, paraganglia formed rounded cellular masses which were frequently in company with the autonomic nerves and ganglia of the urinary bladder and other pelvic viscera. The constituent cells contained only small amounts of cholinesterase and were unrelated to enzyme positive autonomic nerves; acetylcholinesterase containing nerves were occasionally observed in the capsule and the fibrous septa of the pelvic paraganglia. In early postnatal specimens, pelvic paraganglia frequently contained single or multiple pacinian-like corpuscles, each possessing a central region which was rich in both acetyl and pseudocholinesterase. These structures were rarely observed within autonomic ganglia and were absent 4 1/2 years post partum. By means of a histochemical technique, pelvic paraganglia were found to contain catecholamine which was attributed to the presence of relatively large quantities of noradrenaline. These observations have been discussed with particular reference to the results of other studies on the autonomic innervation of paraganglia.     

Oestrus, time of ovulation, ovulation rate and conception rate in progestagen-treated ewes given Gn-RH, Gn-TH analogues and gonadotrophins.

The influence of Gn-RH, hCG and a PMSG-hCG mixture (PG600) on the time of ovulation, ovulation rate and on the occurrence of oestrus in ewes treated with progestagen-impregnated sponges for 12 days examined. The effects of Gn-RH analogues on plasma LH, oestrus, ovulation and conception rate were also investigated. Six separate experiments were carried out. When 50 micrograms Gn-RH were given 24 h after sponge removal ovulation occurred in 44--46% of ewes within 24 h and in all ewes by 34 h. Gn-RH was a more potent ovulation synchronizer than hCG. Both hCG and PG600 reduced the incidence of overt oestrus. Gn-RH also had this effect in ewes treated during February and May but not in August and September. Gn-RH analogues given 2 days before sponge removal significantly increased ovulation rate. The display of oestrus was not affected in ewes treated 2 days before sponge removal but was suppressed in 43-69% of ewes treated with an analogue at the time of sponge removal. Ovulation occurred in 50-62% of ewes within 30-35 h of injection of Gn-RH analogues, regardless of the time of their administration. The release of LH in response to one analogue was not influenced by the presence of the progestagen-impregnated sponge in the vagina. When given a Gn-RH analogue 2 days before sponge removal or at the time of sponge removal 63 and 62% of mated ewes became pregnant compared with 70% of control ewes.     

Population genetic structure of mussels from the Baltic Sea

In a macrogeographic survey, the population genetic structure of mussels from various regions of the Baltic Sea, a large semi-enclosed brackish-water basin, was examined with reference toMytilus edulis andM. galloprovincialis samples from the North Sea, Irish coast and southern Portugal. Electrophoretically detectable variation was analysed at 6 polymorphic enzyme loci (Ap, Est-D, Lap-2, Odh, Pgi andPgm). Evidence was provided of a remarkably large amount of biochemical genetic differentiation among ecologically and morphologically divergent mussel populations in the Baltic. Patterns of allele frequencies in low-salinity populations from the area of the Baltic Proper were demonstrated to be widely homogeneous but contrast strongly with those of the western Baltic, the latter resembling populations from marine habitats of the North Sea. Associated with a pronounced salinity gradient, the spatial heterogeneity in gene-pool structure is indicated by steep clines of allele frequency changes in the area of the eastern Danish isles. The adaptive significance of the observed allozymic variation is suggested. From genetic distance estimates, the subdivision of population structure is discussed in relation to the significant amount of differentiation detected withinMytilus populations to date and to the evolutionary time required for the divergence of Baltic mussel populations. The allozymic data provide evidence for the genetic distinctiveness of mussels from the low-salinity areas of the Baltic. Their position at the specific or subspecific level of classification requires further consideration.     

The economic benefits of malaria elimination: do they include increases in tourism?

ABSTRACT: BACKGROUND: Policy makers have speculated that one of the economic benefits of malaria elimination includes increases in foreign direct investment, particularly tourism. METHODS: The study examines the empirical relationship between the demand for travel and malaria cases in two countries with large tourism industries around the time in which they carried out malaria-elimination campaigns. In Mauritius, this analysis examines historical yearly tourist arrivals and malaria cases from 1978-1999, accounting for the background secular trend of increasing international travel. In Dominican Republic, a country embarking upon malaria elimination, it employs a time-series analyses of the monthly, international, tourist arrivals from 1998-2010 to determine whether the timing of significant deviations in tourist arrivals coincides with malaria outbreaks. RESULTS: While naive relationships exist in both cases, the results show that the relationships between tourist arrival and malaria cases are relatively weak and statistically insignificant once secular confounders are accounted for. CONCLUSIONS: This suggests that any economic benefits from tourism that may be derived from actively pursuing elimination in countries that may have high tourism potential are likely to be small when measured at a national level. Rather, tourism benefits are likely to be experienced with greater impact in more concentrated tourist areas within countries, and future studies should seek to assess this relationship at a regional or local level.