Charles Scott Sherrington (1857–1952) is widely acclaimed as the most important neurophysiologist in history. He became a legend in his own time, coined the term “synapse”, and in 1932 received the ...Nobel Prize in medicine for his discoveries on the function of neurons. By the time he presented the Gifford Lectures 1937–38, he represented the best that science had to offer on behalf of the relationship of the mind to the natural world. The lectures, including one never publicly presented, were published as Man on His Nature (1941). Here neurology meets theology at the busy and often treacherous intersection of science and religion. Examining Sherrington’s views in some detail, the standard rendering of Sherrington as a theist cannot be sustained by their contents; he ends up as at least a humanist and perhaps an atheist. Views by neurologists and philosophers of mind some seventy to eighty years later are compared and contrasted with Sherrington’s. Although expectations of a materialist/reductionist answer to the mind/body problem have not been realized, neuroscientist Raymond Tallis appears as a parallel figure to Sherrington: both are clearly naturalistic humanists. A theistic response is presented addressing the mind/body problem from a hylomorphic process theology perspective, along with some comments regarding natural theology in general. In the end, this essay has two complementary aims: (1) to relocate Sherrington’s neurotheology—if it can be called that—in a more appropriate historiographical category; and (2) to offer a viable answer to the mind/body problem.
Despite his impeccable academic pedigree, a protégé of Josiah Royce and a friend and student of William James, John Elof Boodin is nearly forgotten today among American philosophers; hence, an ...essential aspect of his thought lost to history is his contribution to process theology. The leading features of process thought demonstrate Boodin’s connections to this unique theology and show it to have been established early on, as early as 1900 and 1904. This places Boodin’s writing on process philosophy/theology well before Alfred North Whitehead, the putative pioneer in modern process metaphysics, by more than twenty years, and co-extensive with Henri Bergson, who influenced Whitehead. Nevertheless, when Boodin is discussed today, it is usually as an early pragmatist rather than as a process philosopher. The central claim of this essay argues that Boodin is best understood as a pragmatically influenced process theist, one of the first in a modern context. This historiographical revision will permit a better portrayal of process thought by revealing a more nuanced and pluralistic theological landscape beyond the standard Bergsonian/Whiteheadian/Hartshornian triumvirate.
Context
Transgender men (TGM) are persons assigned female gender at birth with a male gender identity and are routinely treated with testosterone. Androgen excess is associated with endothelial ...dysfunction among cisgender females (CGF) and is an early sign of atherosclerosis and hypertension.
Objective
To determine the effect of testosterone treatment on endothelial function in TGM.
Setting
The John B. Pierce Laboratory and Yale School of Medicine.
Subjects
Eleven TGM (age 27 ± 5 years; BMI 24.4 ± 3.7 kg/m2) receiving testosterone (T) and 20 CGF (28 ± 5 years; BMI 26.0 ± 5.1 kg/m2) during the early follicular phase of their menstrual cycle.
Design and Outcome Measures
We evaluated brachial vasodilatory responses following stimuli designed to elicit shear stress using 5‐minute occlusion to determine endothelial function (flow‐mediated vasodilation, FMD).
Results
Total T was greater in the TGM compared to CGF (484.6 ± 122.5 vs 1.5 ± 0.7 ng/dL), as was free T (83.9 ± 32.4 vs 1.9 ± 0.8 pg/dL). FMD was markedly lower in the TGM (4.5 ± 2.7%) compared to the CGF (8.1 ± 2.9%, P = .002) indicating significantly diminished endothelial function in TGM.
Conclusions
We have shown for the first time that in TGM the androgen‐dominant hormonal milieu was associated with impaired endothelial function. Endothelial dysfunction precedes clinically detectable atherosclerotic plaque in the coronary arteries, so is an important marker for clinical cardiovascular risk. Therefore, attention to cardiovascular risk factors should be integral to the care of transgender men.
Alfred Russel Wallace’s conception of evolution and its relation to natural theology is examined. That conception is described as intelligent evolution—directed, detectably designed, and purposeful ...common descent. This essay extends discussion of the forces and influences behind Wallace’s journey from the acknowledged co-discoverer of natural selection, to include his much lesser known position within the larger history of natural theology. It will do so by contextualizing it with an analysis of Darwin’s metaphysical commitments identified as undogmatic atheism. In this sense, David Kohn’s thesis that Darwin was the “last of the natural theologians” is revised to suggest that Wallace deserves to be included within the larger context of the British natural theologians in a surprisingly Paleyan tradition. As such, an important object of this essay is to clear away the historical fog that has surrounded this aspect of Wallace. That “fog” is composed of various formal historical fallacies that will be outlined in the penultimate section. Once described, explained, and corrected, Wallace becomes an enduring figure in carrying the British tradition of natural theology into the twentieth century and beyond.
It is often assumed that direction and purpose in nature—teleology—is a dead relic of the past, a result of Charles Darwin’s Origin of Species (1859) and Descent of Man (1871). But teleology has had ...a long and complex relationship with science. This paper will trace its general history with an emphasis upon the life sciences, especially biology. Particularly important is the fact that all teleology is not equal; strong (transcendent) teleology (designated Ts) should be distinguished from weak (purely descriptive and utilitarian) teleology (designated Tw). A working definition of teleology in its most meaningful aspects is then given. The challenges that Darwinism faced in dealing with purpose in nature are discussed, as is their proposed solution in the evolutionary synthesis, and the persistence of Ts following that synthesis is outlined and critiqued. Evidence of Ts persistence in the life sciences is presented with several relevant examples, and strong teleology is further differentiated by specific (Ts+) and nonspecific (Ts−) varieties. This essay concludes that Ts remains an ongoing and integral part of the life sciences and will likely remain so, even though it may be true but not verifiable empirically.
Provides a critical reassessment of Alfred Russel Wallace's path to natural theology and counters the dismissive narrative that Wallace's theistic and sociopolitical positions are not to be taken ...seriously in the history and philosophy of science.
Background: Recent clinical trials and case‐reports indicate that baclofen, a GABAB agonist, may have efficacy for alcohol dependence. Baclofen has been shown to enhance abstinence, to reduce ...drinking quantity, to reduce craving, and to reduce anxiety in alcohol‐dependent individuals in 2 placebo‐controlled trials in Italy. However, the clinical trial data with baclofen is limited. The purpose of the present study was to test the efficacy and tolerability of baclofen in alcohol dependence in the United States.
Methods: The study was a double‐blind, placebo‐controlled, randomized study comparing 30 mg/d of baclofen to placebo over 12 weeks of treatment and utilizing 8 sessions of BRENDA, a low‐intensity psychosocial intervention. One hundred and twenty‐one subjects were screened to yield 80 randomized subjects (44 men) with randomization balanced for gender. Percent heavy drinking days was the primary outcome measure with other drinking outcomes, anxiety levels, and craving as secondary outcomes. Tolerability was examined.
Results: Seventy‐six percent of subjects completed the study. No difference by drug condition was seen in percentage of heavy drinking days where on‐average rates were 25.5% (±23.6%) for placebo and 25.9% (±23.2%) for baclofen during treatment (t73 = 0.59, p = 0.56). Similarly, no differences were seen by drug condition in percentage of days abstinent, time to first drink, or time to relapse to heavy drinking. Baclofen was associated with a significant reduction in state anxiety (F1,73 = 5.39, p = 0.02). Baclofen was well tolerated with only 2 individuals stopping baclofen because of adverse events. There were no serious adverse events.
Conclusions: Baclofen, a GABAB agonist, represents a possible new pharmacotherapeutic approach to alcohol dependence. Despite encouraging preclinical data and prior positive clinical trials with baclofen in Italy, the current trial did not find evidence that baclofen is superior to placebo in the treatment of alcohol dependence. Additional clinical trial work is necessary to establish whether baclofen does or does not have therapeutic efficacy in alcohol dependence and, if it does, what factors are predictive of response.
This study uses skeletal variations in coral Sr/Ca from three Siderastrea siderea coral colonies within the Dry Tortugas National Park in the southeastern Gulf of Mexico (24°42′N, 82°48′W) to ...reconstruct monthly sea surface temperature (SST) variations from 1734 to 2008 Common Era (C.E.). Calibration and verification of the replicated coral Sr/Ca‐SST reconstruction with local, regional, and historical temperature records reveals that this proxy‐temperature relationship is stable back to 1879 C.E. The coral SST reconstruction contains robust interannual (~2.0°C) and multidecadal variability (~1.5°C) for the past 274 years, the latter of which does not covary with the Atlantic Multidecadal Oscillation. Winter SST extremes are more variable than summer SST extremes (±2.2°C versus ±1.6°C, 2σ) suggesting that Loop Current transport in the winter dominates variability on interannual and longer time scales. Summer SST maxima are increasing (+1.0°C for 274 years, σMC = ±0.5°C, 2σ), whereas winter SST minima contain no significant trend. Colder decades (~1.5°C) during the Little Ice Age (LIA) do not coincide with decades of sunspot minima. The coral SST reconstruction contains similar variability to temperature reconstructions from the northern Gulf of Mexico (planktic foraminifer Mg/Ca) and the Caribbean Sea (coral Sr/Ca) suggesting areal reductions in the Western Hemisphere Warm Pool during the LIA. Mean summer coral SST extremes post‐1985 C.E. (29.9°C) exceeds the long‐term summer average (29.2°C for 1734–2008 C.E.), yet the warming trend after 1985 C.E. (0.04°C for 24 years, σMC = ±0.5, 2σ) is not significant, whereas Caribbean coral Sr/Ca studies contain a warming trend for this interval.
Key Points
Calibration of coral Sr/Ca to sea surface temperature is stable for 130 years
Summer SST extremes are warming, whereas winter SST extremes are more variable
Coral SST records suggest reduced Western Hemisphere Warm Pool in Little Ice Age
Problem
Diabetes confers an increased risk of preeclampsia, but its pathogenic role in preeclampsia is poorly understood. The objective of this study was to elucidate the effects of excess glucose on ...trophoblast function and whether any changes could be reversed by metformin.
Method of study
The human first trimester trophoblast cell line (Sw.71) was treated with glucose at 5, 10, 25, and 50 mm, in the presence and absence of metformin. Trophoblast migration was quantified and supernatant cytokine, chemokine, and angiogenic factors measured.
Results
Increasing concentrations of glucose significantly increased trophoblast secretion of the inflammatory cytokines/chemokines: IL‐1β, IL‐6, IL‐8, GRO‐α, RANTES, and G‐CSF; significantly increased trophoblast secretion of the anti‐angiogenic factors sFlt‐1 and sEndoglin; and significantly decreased trophoblast migration. Excess glucose‐induced trophoblast IL‐1β production was inhibited by disabling the Nalp3/ASC inflammasome. Metformin partially reduced the glucose‐induced inflammatory response, but had no effect on the anti‐angiogenic or antimigratory response.
Conclusion
Excess glucose induced a pro‐inflammatory, anti‐angiogenic, and antimigratory state in first trimester trophoblast cells. Glucose‐induced trophoblast IL‐1β secretion was mediated by the inflammasome. Glucose‐induced inflammation was partially reversed by metformin. These findings demonstrate the pleiotropic effects of hyperglycaemia on the trophoblast, providing potential explanations for the strong link between diabetes and preeclampsia.
Endometrial cancer develops during exposure to estrogen unopposed by progesterone. Traditional formulations for menopausal hormone therapy include a progestin in women with a uterus. However, ...progestin exposure increases breast cancer risk in postmenopausal women. Alternatives to progestin include bazedoxifene (BZA), a selective estrogen receptor modulator, which prevents estrogen induced endometrial hyperplasia in clinical trials. Molecular mechanisms responsible for BZA's antiproliferative effect are not fully elucidated. We profiled endometrial adenocarcinoma, hyperplasia, and normal proliferative endometrium for differential expression in genes known to be regulated by estrogens or progesterone. Fibroblast growth factor (FGF)18, a paracrine growth factor promoting epithelial proliferation, was significantly increased in adenocarcinoma. Progesterone represses FGF18 by inducing heart and neural crest derivatives expressed transcript 2 (HAND2) in stromal cells. Notably, we confirmed lower HAND2 mRNA in adenocarcinoma, along with higher FGF tyrosine kinase receptor 2 and E74-like factor 5, collectively promoting FGF18 activity. We hypothesized BZA reduces epithelial proliferation by inhibiting FGF18 synthesis in stromal cells. To determine whether BZA regulates FGF18, we treated primary stromal cells with BZA or vehicle. In vitro, BZA reduced FGF18, but did not affect, HAND2. CD1 female mice received either BZA, conjugated estrogen (CE), or combined BZA/CE for 8 weeks. CE-treated mice had nearly 3-fold higher FGF18 expression. In contrast, BZA-treated mice, alone or with CE, had similar FGF18 as controls. Unexpectedly, BZA, alone or with CE, reduced HAND2 more than 80%, differing from progesterone regulation. Reduction of FGF18 is a potential mechanism by which BZA reduces endometrial proliferation and hyperplasia induced by estrogens. However, BZA works independently of HAND2, revealing a novel mechanism for progestin-free hormone therapy in postmenopausal women.
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