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Introduction: Blood-based Alzheimer's disease (AD) biomarkers show promise, but pre-analytical protocol differences may pose problems. We examined seven AD blood biomarkers (amyloid beta [ A β ] 42 , A β 40 , phosphorylated tau [ p - ta u 181 , total tau [t-tau], neurofilament light chain [NfL], A β 42 40 , and p - ta u 181 A β 42 ) in three collection tube types (ethylenediaminetetraacetic acid [EDTA] plasma, heparin plasma, serum)., Methods: Plasma and serum were obtained from cerebrospinal fluid or amyloid positron emission tomography-positive and -negative participants (N = 38) in the Wisconsin Registry for Alzheimer's Prevention. We modeled AD biomarker values observed in EDTA plasma versus heparin plasma and serum, and assessed correspondence with brain amyloidosis., Results: Results suggested bias due to tube type, but crosswalks are possible for some analytes, with excellent model fit for NfL ( R 2 = 0.94), adequate for amyloid ( R 2 = 0.40-0.69), and weaker for t-tau ( R 2 = 0.04-0.42) and p - ta u 181 ( R 2 = 0.22-0.29). Brain amyloidosis differentiated several measures, especially EDTA plasma pTa u 181 A β 42 ( d = 1.29)., Discussion: AD biomarker concentrations vary by tube type. However, correlations for some biomarkers support harmonization across types, suggesting cautious optimism for use in banked blood., Competing Interests: SCJ serves on an advisory board for Roche Diagnostics. KB has served as a consultant, on advisory boards, or on data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, all unrelated to the present study. HZ has served on scientific advisory boards for Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, and CogRx; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, and Biogen; and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). BB has received precursors and tracers from Avid Radiopharmaceuticals. CEG is a member of the Executive Board for the Alzheimer's and Dementia Alliance of Wisconsin, and receives support from the Alzheimer's Association for travel to AAIC, for which she is on the Scientific Program Committee. GK is a full‐time employee of Roche Diagnostics GmbH. IS is a full‐time employee and shareholder of Roche Diagnostics International Ltd. Authors KH, CE, OO, TB, CVH, RK, LH, and EMJ have no disclosures., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

The urgency of the climate and sustainability crises and their health effects are receiving increasing attention in the German health system. To avoid further exacerbation of these crises, profound transformative processes in all sectors of society are needed (e.g. transport, energy production, and food systems). Based on the ethical imperative of non-maleficence and the high levels of trust in society, health professionals have great potential to make an important contribution to the necessary transformative processes.In order to fully harness this potential, health professionals should be supported in developing competencies to take transformative action during their pre- and postgraduate education and professional training. In this article, we introduce the concept of planetary health, as this concept provides orientation for this both ethically and with regards to the subject matter. Furthermore, we provide an overview of current teaching and learning formats and identify aspects that could contribute to further developing planetary health education.

Rationale: Cardiomyocytes cultured in a mechanically active 3-dimensional configuration can be used for studies that correlate contractile performance to cellular physiology. Current engineered cardiac tissue (ECT) models use cells derived from either rat or chick hearts. Development of a murine ECT would provide access to many existing models of cardiac disease and open the possibility of performing targeted genetic manipulation with the ability to directly assess contractile and molecular variables., Objective: To generate, characterize, and validate mouse ECT with a physiologically relevant model of hypertrophic cardiomyopathy., Methods and Results: We generated mechanically integrated ECT using isolated neonatal mouse cardiac cells derived from both wild-type and myosin-binding protein C (cMyBP-C)-null mouse hearts. The murine ECTs produced consistent contractile forces that followed the Frank-Starling law and accepted physiological pacing. cMyBP-C-null ECTs showed characteristic acceleration of contraction kinetics. Adenovirus-mediated expression of human cMyBP-C in murine cMyBP-C-null ECT restored contractile properties to levels indistinguishable from those of wild-type ECT. Importantly, the cardiomyocytes used to construct the cMyBP-C(-/-) ECT had yet to undergo the significant hypertrophic remodeling that occurs in vivo. Thus, this murine ECT model reveals a contractile phenotype that is specific to the genetic mutation rather than to secondary remodeling events., Conclusions: Data presented here show mouse ECT to be an efficient and cost-effective platform to study the primary effects of genetic manipulation on cardiac contractile function. This model provides a previously unavailable tool to study specific sarcomeric protein mutations in an intact mammalian muscle system.

Linking client data across care sectors and agencies is becoming essential to ensure continuity of care, evaluation, and planning of mental health services delivery. The Data Linkage System (DLS), a record-linked, client-based, mental health database in northwestern Ontario, was established in response to this need. It is a voluntary system currently used by 30 of 40 mental health programs. The study surveyed program administrators to determine the system's utilization, perceived value, and future needs regarding data collection. The survey results delineated the perceived usefulness of the DLS in a remote region. The findings will provide direction for continued development of the DLS.

B6.129S7-Gtrosa26 (ROSA26) mice carry a LacZ-neo(R) insertion on Chromosome (Chr) 6, made by promoter trapping with AB1 129 ES cells. Female C57BL/6J Apc(Min/+) (B6 Min/+) mice are very susceptible to the induction of mammary tumors after treatment with ethylnitrosourea (ENU). However, ENU-treated B6 mice carrying both Apc(Min) and ROSA26 are resistant to mammary tumor formation. Thus, ROSA26 mice carry a modifier of Min-induced mammary tumor susceptibility. We have previously mapped the modifier to a 4-cM interval of 129-derived DNA that also contains the ROSA26 insertion. Here we report additional evidence for the effect of the ROSA26 insertion on mammary tumor formation. To test the hypothesis that the resistance was due to a linked modifier locus, we utilized two approaches. We have derived and tested two lines of mice that are congenic for 129-derived DNA within the minimal modifier interval and show that they are as susceptible to mammary tumors as are B6 mice. Additionally, we analyzed a backcross population segregating for the insertion and show that mice carrying the insertion are more resistant to mammary tumor development than are mice not carrying the insertion. Thus, the resistance is not due to a 129-derived modifier allele, but must be due to the ROSA26 insertion. In addition, the effect of the ROSA26 insertion can be detected in a backcross population segregating for other mammary modifiers.

Treatment of female C57BL/6J (B6) mice carrying the mutant Min allele of the adenomatous polyposis coli (Apc) gene with ethylnitrosourea (ENU) results in approximately 90% of mice developing an average of three mammary tumors within 65 days. As a first step in the identification of loci modifying susceptibility to ENU-induced mammary tumors and hyperplasias, we have tested ENU-treated Apc(Min)/+ (Min/+) mice on several hybrid backgrounds for susceptibility to mammary and intestinal tumors. C57BR/cdJxB6 (BRB6) Min/+ mice were more sensitive to development of mammary squamous cell carcinomas than B6 Min/+ mice. In contrast, Min/+ hybrids between B6 and FVB/NTac (FVB), 129X1/SvJ (129X1), and 129S6/SvEvTac (129S6) were all significantly more resistant to mammary carcinoma development. However, mice from these three crosses developed more focal mammary hyperplasias than did the B6 or BRB6 Min/+ mice. Susceptibility to intestinal tumors was independent of mammary tumor susceptibility in most hybrids. These results indicate that genetic background can affect independently the phenotypes conferred by the Min allele of APC:

B6.129S7-Gtrosa26 (B6.R26) mice carry a LacZ-neoR insertion on Chromosome (Chr) 6, made by promoter trapping with 129 ES cells. Female C57BL/6J ApcMin/+ (B6Min/+) mice are highly susceptible to intestinal tumors and to the induction of mammary tumors after treatment with ethylnitrosourea (ENU). However, B6.R26/+ Min/+ females develop fewer mammary and intestinal tumors after ENU treatment than do B6 Min/+ mice. B6.R26/+ mice from two independently derived congenic lines show this modifier effect. Each of these congenic lines carries approximately 20 cM of 129-derived DNA flanking the insertion, raising the possibility that the resistance is due to a linked modifier locus. To further map the modifier locus, we have generated several lines of mice carrying different regions of the congenic interval. We have found that resistance to mammary and intestinal tumors in ENU-treated Min/+ mice maps to a minimum 4-cM interval that includes the ROSA26 LacZ-neoR insertion. Therefore, the resistance to tumor development is due to either the ROSA26 insertion or a very tightly linked modifier locus.

Serum LH changes in response to LH-RH injection were measured in intact and ovariectomized, steroid-treated female rats which were androgenized neonatally with 1,250 microgram testosterone propionate (TP) on day 5. At a dose of 20 ng LH-RH/100 g b.w., serum LH levels in intact rats increased over pre-injection levels, and at a dose of 100 ng LH-RH/100 g b.w., LH concentrations 15 min after injection were higher in nembutal-blocked proestrous rats than in androgen-sterilized rats. However, the ovulation response was not different between the groups. In ovariectomized estradiol benzoate (EB)-treated, androgen-sterilized rats, serum LH concentrations 15 and 60 min after LH-RH injection were lower than in similarly treated control rats. This effect was not secondary to the anovulatory state of the animal, since it also occurred in ovariectomized EB-treated prepuberal rats and in rats ovariectomized prepuberally and treated with EB in adulthood. Also, after treatment with 5alpha-dihydrotestosterone propionate (5alpha-DHTP), pituitary responsiveness to LH-RH in androgen-sterilized rats was lower than in control rats, which suggests that the subnormal response in the estrogen-treated rats was not due to a relative insensitivity to estrogen in the androgen-sterilized rats. The relatively high pituitary responsiveness to LH-RH in intact androgen-sterilized rats is probably due to the high circulating estrogen levels. The subnormal pituitary responsiveness to LH-RH after ovariectomy and estradiol treatment suggests, in addition to an effect on the hypothalamus, also a direct effect of neonatal androgen administration on the pituitary.

A possible role of 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-androstanediol) in the control of FSH secretion was studied at various ages in ovariectomized rats. In the rat strain used, vaginal opening, coincident with first ovulation, generally occurs between 37 and 42 days of age. If 3 alpha-androstanediol alone was given as an ovarian substitute, an inhibitory effect on FSH release was evident with all three doses tested (50, 100, 300 microgram/100 g body wt) between 13 and 30 days of age; at 33-35 days of age only the 300 microgram dose caused some inhibition of FSH release. Results were more complex if 3 alpha-androstanediol was given in combined treatment with oestradiol and progesterone. Given with progesterone, 3 alpha-androstanediol showed a synergistic inhibitory action on FSH release between 20 and 30 days of age. However, when 3 alpha-androstanediol was combined with oestradiol a clear decrease in effect, as compared to the effect of oestradiol alone, was found between 20 and 30 days of age. Also the effect of combined oestradiol and progesterone treatment was greater than the effect of combined treatment with oestradiol, progesterone and 3 alpha-androstanediol. At all ages after day 20 none of the steroid combinations tested was capable of maintaining FSH levels in ovariectomized rats similar to those in intact rats. It is concluded that 3 alpha-androstanediol might play a role in the control of FSH secretion in the immature rat, but after day 20 the potentially inhibitory action of 3 alpha androstanediol on FSH secretion is limited in the presence of oestradiol.

The high amounts of 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) present in immature female rats decline towards first ovulation, but on the day of first proestrus a peak is seen. This raises the possibility that during adulthood similar proestrous peaks may occur. Therefore, serum concentrations and ovarian content of 3 alpha-diol were estimated every two hours between 0900 and 2100 h in adult cyclic rats on the day of proestrus. In the same rats, serum concentrations of estradiol (E2), progesterone (P) and luteinizing hormone (LH) were measured, as were ovarian contents of E2 and P. A significant elevation in ovarian 3 alpha-diol was found between 0900 and 1700 h proestrus, whereas serum concentrations of 3 alpha-diol were elevated from 1300 to 2100 h. The high morning values of ovarian 3 alpha-diol correlated with those for ovarian E2 (p less than 0.005); the elevated serum concentrations of 3 alpha-diol during the afternoon correlated with serum P (p less than 0.005) and with serum LH concentrations (p less than 0.005). Serum and ovarian values were positively correlated for P and E2, but not for 3 alpha-diol. The rise in serum 3 alpha-diol could be prevented by blocking the LH surge with sodium pentobarbitone (Nembutal; 35 mg/kg b.w.) administered at 1300 h. In Nembutal-treated rats, the concentration of 3 alpha-diol at 1700 h (886 pg/ml) was significantly lower than in saline-treated control rats (1135 pg/ml; p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)