Clinical Therapeutics in Pregnancy

Most drugs are not tested for use during pregnancy, consequently, labeling, which may include information about fetal safety, includes nothing about dosing, efficacy, or maternal safety. Yet these are concerns of health care providers considering treatment of disease during pregnancy. Therefore, the practitioner treats the pregnant woman with the same dose recommended for use in adults (typically men) or may decide not to treat the disease at all. However, is the choice of not treating a woman during pregnancy better than dealing with the challenges which accompany treatment? This paper, which summarizes metabolic and physiologic changes induced by pregnancy, illustrates that standard adult dosing is likely to be incorrect during pregnancy

Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function

Peripheral processes that mediate beneficial effects of exercise on the brain remain sparsely explored. Here, we show that a muscle secretory factor, cathepsin B (CTSB) protein, is important for the cognitive and neurogenic benefits of running. Proteomic analysis revealed elevated levels of CTSB in conditioned medium derived from skeletal muscle cell cultures treated with AMP-kinase agonist AICAR. Consistently, running increased CTSB levels in mouse gastrocnemius muscle and plasma. Furthermore, recombinant CTSB application enhanced expression of brain-derived neurotrophic factor (BDNF) and doublecortin (DCX) in adult hippocampal progenitor cells through a mechanism dependent on the multifunctional protein P11. In vivo, in CTSB knockout (KO) mice, running did not enhance adult hippocampal neurogenesis and spatial memory function. Interestingly, in Rhesus monkeys and humans, treadmill exercise elevated CTSB in plasma. In humans, changes in CTSB levels correlated with fitness and hippocampus-dependent memory function. Our findings suggest CTSB as a mediator of effects of exercise on cognition

Understanding the conditions that influence the roles of midwives in Ontario, Canada’s health system: an embedded single-case study

Abstract: Background: Despite the significant variability in the role and integration of midwifery across provincial and territorial health systems, there has been limited scholarly inquiry into whether, how and under what conditions midwifery has been assigned roles and integrated into Canada’s health systems. Methods: We use Yin’s (2014) embedded single-case study design, which allows for an in-depth exploration to qualitatively assess how, since the regulation of midwives in 1994, the Ontario health system has assigned roles to and integrated midwives as a service delivery option. Kingdon’s agenda setting and 3i + E theoretical frameworks are used to analyze two recent key policy directions (decision to fund freestanding midwifery-led birth centres and the Patients First primary care reform) that presented opportunities for the integration of midwives into the health system. Data were collected from key informant interviews and documents. Results: Nineteen key informant interviews were conducted, and 50 documents were reviewed in addition to field notes taken during the interviews. Our findings suggest that while midwifery was created as a self-regulated profession in 1994, health-system transformation initiatives have restricted the profession’s integration into Ontario’s health system. The policy legacies of how past decisions influence the decisions possible today have the most explanatory power to understand why midwives have had limited integration into interprofessional maternity care. The most important policy legacies to emerge from the analyses were related to payment mechanisms. In the medical model, payment mechanisms privilege physician-provided and hospital-based services, while payment mechanisms in the midwifery model have imposed unintended restrictions on the profession’s ability to practice in interprofessional environments. Conclusions: This is the first study to explain why midwives have not been fully integrated into the Ontario health system, as well as the limitations placed on their roles and scope of practice. The study also builds a theoretical understanding of the integration process of healthcare professions within health systems and how policy legacies shape service delivery options

A critical interpretive synthesis of the roles of midwives in health systems

Abstract: Please refer to full text to view abstract

Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

Shadowing, Binding and Off-Shell Effects in Nuclear Deep Inelastic Scattering

We present a unified description of nuclear deep inelastic scattering (DIS) over the whole region $0<x<1$ of the Bjorken variable. Our approach is based on a relativistically covariant formalism which uses analytical properties of quark correlators. In the laboratory frame it naturally incorporates two mechanisms of DIS: (I) scattering from quarks and antiquarks in the target and (II) production of quark-antiquark pairs followed by interactions with the target. We first calculate structure functions of the free nucleon and develop a model for the quark spectral functions. We show that mechanism (II) is responsible for the sea quark content of the nucleon while mechanism (I) governs the valence part of the nucleon structure functions. We find that the coherent interaction of $\bar qq$ pairs with nucleons in the nucleus leads to shadowing at small $x$ and discuss this effect in detail. In the large $x$ region DIS takes place mainly on a single nucleon. There we focus on the derivation of the convolution model. We point out that the off-shell properties of the bound nucleon structure function give rise to sizable nuclear effects.Comment: 29 pages (and 10 figures available as hard copies from Authors), REVTE

Religiosity is associated with greater size, kin density, and geographic dispersal of women's social networks in Bangladesh

Human social relationships, often grounded in kinship, are being fundamentally altered by globalization as integration into geographically distant markets disrupts traditional kin based social networks. Religion plays a significant role in regulating social networks and may both stabilize extant networks as well as create new ones in ways that are under-recognized during the process of market integration. Here we use a detailed survey assessing the social networks of women in rural Bangladesh to examine whether religiosity preserves bonds among kin or broadens social networks to include fellow practitioners, thereby replacing genetic kin with unrelated co-religionists. Results show that the social networks of more religious women are larger and contain more kin but not more non-kin. More religious women's networks are also more geographically diffuse and differ from those of less religious women by providing more emotional support, but not helping more with childcare or offering more financial assistance. Overall, these results suggest that in some areas experiencing rapid social, economic, and demographic change, religion, in certain contexts, may not serve to broaden social networks to include non-kin, but may rather help to strengthen ties between relatives and promote family cohesion

Leptoproduction of Heavy Quarks II -- A Unified QCD Formulation of Charged and Neutral Current Processes from Fixed-target to Collider Energies

A unified QCD formulation of leptoproduction of massive quarks in charged current and neutral current processes is described. This involves adopting consistent factorization and renormalization schemes which encompass both vector-boson-gluon-fusion (flavor creation) and vector-boson-massive-quark-scattering (flavor excitation) production mechanisms. It provides a framework which is valid from the threshold for producing the massive quark (where gluon-fusion is dominant) to the very high energy regime when the typical energy scale \mu is much larger than the quark mass m_Q (where the quark-scattering should be prevalent). This approach effectively resums all large logarithms of the type (alpha_s(mu) log(mu^2/m_Q^2)^n which limit the validity of existing fixed-order calculations to the region mu ~ O(m_Q). We show that the (massive) quark-scattering contribution (after subtraction of overlaps) is important in most parts of the (x, Q) plane except near the threshold region. We demonstrate that the factorization scale dependence of the structure functions calculated in this approach is substantially less than those obtained in the fixed-order calculations, as one would expect from a more consistent formulation.Comment: LaTeX format, 29 pages, 11 figures. Revised to make auto-TeX-abl

When a calorie is not just a calorie : Diet quality and timing as mediators of metabolism and healthy aging

Funding Information: We thank Dr. Yih-Woei Fridell of the National Institute on Aging for organizing the meeting, as well as the NIA Division of Aging Biology for their support. We thank Dr. Gino Cortopassi for his edits and suggestions. The figures were created with BioRender.com. The Mihaylova lab is supported in part by the NIA (R00AG054760), Office of the NIH Director (DP2CA271361), the American Federation for Aging Research, the V Foundation, Pew Biomedical Scholar award, and startup funds from the Ohio State University. The Delibegovic lab is funded by the British Heart Foundation, Diabetes UK, BBSRC, NHS Grampian, Tenovus Scotland, and the Development Trust (University of Aberdeen). J.J.R. is supported by NIA PO1AG062817, R21AG064290, and R21AG071156. Research support for J.B. was from NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01DK127800, R01DK113011, R01DK090625, and R01DK050203 and the National Institute on Aging (NIA) grants R01AG065988 and P01AG011412, as well as the University of Chicago Diabetes Research and Training Center grant P30DK020595. This work was supported by NIH grants AG065992 to G.M. and AG068550 to G.M. and S.P. as well as UAB Startup funds 3123226 and 3123227 to G.M. R.S. is supported by NIH grants RF1AG043517, R01AG065985, R01DK123327, R56AG074568, and P01AG031782. Z.C. is primarily funded by The Welch Foundation (AU-1731-20190330) and NIH/NIA (R01AG065984, R56AG063746, RF1AG061901, and R56AG076144). A.C. is supported by NIA grant R01AG065993. W.W.J. is supported by the NIH (R01DC020031). M.S.-H. is supported by NIH R01 R35GM127049, R01 AG045842, and R21 NS122366. The research in the Dixit lab was supported in part by NIH grants AG031797, AG045712, P01AG051459, AR070811, AG076782, AG073969, and AG068863 and Cure Alzheimer's Fund (CAF). A.E.T.-M. is supported by the NIH/NIA (AG075059 and AG058630), NIAMS (AR071133), NHLBI (HL153460), pilot and feasibility funds from the NIDDK-funded UAB Nutrition Obesity Research Center (DK056336) and the NIA-funded UAB Nathan Shock Center (AG050886), and startup funds from UAB. J.A.M. is supported by the Intramural Research Program, NIA, NIH. The Panda lab is supported by the NIH (R01CA236352, R01CA258221, RF1AG068550, and P30CA014195), the Wu Tsai Human Performance Alliance, and the Joe and Clara Tsai Foundation. The Lamming lab is supported in part by the NIA (AG056771, AG062328, AG061635, and AG081482), the NIDDK (DK125859), startup funds from UW-Madison, and the U.S. Department of Veterans Affairs (I01-BX004031), and this work was supported using facilities and resources from the William S. Middleton Memorial Veterans Hospital. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work does not represent the views of the Department of Veterans Affairs or the United States Government. D.W.L. has received funding from, and is a scientific advisory board member of, Aeovian Pharmaceuticals, which seeks to develop novel, selective mTOR inhibitors for the treatment of various diseases. S.P. is the author of the books The Circadian Code and The Circadian Diabetes Code. Funding Information: We thank Dr. Yih-Woei Fridell of the National Institute on Aging for organizing the meeting, as well as the NIA Division of Aging Biology for their support. We thank Dr. Gino Cortopassi for his edits and suggestions. The figures were created with BioRender.com . The Mihaylova lab is supported in part by the NIA ( R00AG054760 ), Office of the NIH Director ( DP2CA271361 ), the American Federation for Aging Research , the V Foundation , Pew Biomedical Scholar award, and startup funds from the Ohio State University . The Delibegovic lab is funded by the British Heart Foundation , Diabetes UK , BBSRC , NHS Grampian , Tenovus Scotland , and the Development Trust ( University of Aberdeen ). J.J.R. is supported by NIA PO1AG062817 , R21AG064290 , and R21AG071156 . Research support for J.B. was from NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01DK127800 , R01DK113011 , R01DK090625 , and R01DK050203 and the National Institute on Aging (NIA) grants R01AG065988 and P01AG011412 , as well as the University of Chicago Diabetes Research and Training Center grant P30DK020595 . This work was supported by NIH grants AG065992 to G.M. and AG068550 to G.M. and S.P., as well as UAB Startup funds 3123226 and 3123227 to G.M. R.S. is supported by NIH grants RF1AG043517 , R01AG065985 , R01DK123327 , R56AG074568 , and P01AG031782 . Z.C. is primarily funded by The Welch Foundation ( AU-1731-20190330 ) and NIH/NIA ( R01AG065984 , R56AG063746 , RF1AG061901 , and R56AG076144 ). A.C. is supported by NIA grant R01AG065993 . W.W.J. is supported by the NIH ( R01DC020031 ). M.S.-H. is supported by NIH R01 R35GM127049 , R01 AG045842 , and R21 NS122366 . The research in the Dixit lab was supported in part by NIH grants AG031797 , AG045712 , P01AG051459 , AR070811 , AG076782 , AG073969 , and AG068863 and Cure Alzheimer's Fund (CAF). A.E.T.-M. is supported by the NIH/NIA ( AG075059 and AG058630 ), NIAMS ( AR071133 ), NHLBI ( HL153460 ), pilot and feasibility funds from the NIDDK -funded UAB Nutrition Obesity Research Center ( DK056336 ) and the NIA -funded UAB Nathan Shock Center ( AG050886 ), and startup funds from UAB . J.A.M. is supported by the Intramural Research Program, NIA, NIH . The Panda lab is supported by the NIH ( R01CA236352 , R01CA258221 , RF1AG068550 , and P30CA014195 ), the Wu Tsai Human Performance Alliance , and the Joe and Clara Tsai Foundation . The Lamming lab is supported in part by the NIA ( AG056771 , AG062328 , AG061635 , and AG081482 ), the NIDDK ( DK125859 ), startup funds from UW-Madison , and the U.S. Department of Veterans Affairs ( I01-BX004031 ), and this work was supported using facilities and resources from the William S. Middleton Memorial Veterans Hospital. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work does not represent the views of the Department of Veterans Affairs or the United States Government.Peer reviewedPostprin