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Saturday, April 1, 2023

Americans lost a lot of financial ground last year. Is the worst over?

 Americans have been falling behind financially over the last year. Two reports released Thursday show just how much.

The share of Americans who feel financially healthy declined by a whopping nine percentage points in March from a year ago, according to a J.D. Power 2023 U.S. Retail Banking Satisfaction Study, while the percentage of consumers who feel financially vulnerable increased by eight percentage points.

Add to that a chart from Evercore ISI Research and the picture is even grimmer.

It (below) shows how the excess savings Americans built up during the pandemic continues to shrink, falling to levels similar to the third quarter of 2020.

(Credit: Evercore ISI Research)
(Credit: Evercore ISI Research)

Still, there are signs the worst could be over as inflation continues to ease and the job market remains robust.

“We have seen a pretty steep decline in financial health in consumers. There’s a lot more financial stress on consumers, and yes, it’s inflation — [loss of] Covid supports plus inflation,” Paul McAdam, senior director of banking at J.D. Power, told Yahoo Finance. “But consumers’ financial health has stabilized these last few months, so that is positive.”

The big reason folks are feeling more financially stressed is due to cash reserve issues, McAdam said. In the J.D. Power survey, fewer Americans reported they had funds to cover six months of expenses and fewer said they had money stashed away for longer-term needs.

The share of bank customers with more than $10,000 in deposit balances at their main bank declined to 28% in March from 44% a year ago, while the percentage with less than $1,000 jumped to 30% from 17% year over year, according to J.D. Power’s findings.

“The savings cushion they had during Covid is long gone,” McAdam said, echoing the Evercore chart, which showed aggregate savings dropping from a high of $2.3 trillion in the third quarter of 2021 to $1.2 trillion now.

Additionally, more Americans told J.D. Power they could not always pay their bills on time and fewer said they had an excellent credit score. That dovetails with recent data showing that consumers are piling on credit card debt — which hit an all-time high in the fourth quarter of last year — as well as missing payments more often.

The J.D. Power survey did find some bright spots. While only 35% of folks felt financially healthy in March, that’s up from 29% who felt that way in November 2022.

“The low point in the last two years,” McAdam said.

Even the decline in deposits of $10,000 or more has a silver lining, according to McAdam. While Americans are spending down that cushion, they are also moving their money around more to capture better yields on deposit accounts. (The survey, which was conducted before the banking crisis unfolded, doesn’t take into account the $120 billion in deposits that left small and mid-sized banks during the turmoil.)

Still, there’s a ways to go to get back to the nearly 50% of people who felt financially healthy three years ago right as the pandemic began. But some of the pieces are in place. Jobs remain abundant and inflation is going the right way.

“Inflation seems to no longer be accelerating," McAdam said, "so that should help that number move up."

https://finance.yahoo.com/news/americans-lost-a-lot-of-financial-ground-last-year-is-the-worst-over-185952078.html

Effectiveness of lactation cookies on human milk production

 They sell worldwide, often retailing for more than $2.50 per two-ounce bag: Lactation cookies, which manufacturers purport to increase milk in people who breastfeed. Many claim they work—but what does the science say?

Several esteemed nutrition researchers collaborated on "Effectiveness of Lactation Cookies on Human Milk Production Rates: A Randomized Controlled Trial," recently published in The American Journal of Clinical Nutrition.

David B. Allison, Ph.D., dean of the Indiana University School of Public Health-Bloomington (SPH-B), is among the researchers who conducted a one-month,  of lactating parents of healthy babies in the same age range. Their findings revealed no evidence for an effect of consuming lactation cookies on human milk production.

"Too often in the field of nutrition and food, strong beliefs—sometimes even well-reasoned conjectures based upon some —are mistaken for demonstrated facts," Allison said. "Conjecture is good, but knowing is better. We come to know about the effects of nutrition and  through rigorous, randomized, controlled trials. Having conducted such a study on lactation cookies, we found no evidence for their effectiveness.

"This does not mean that it is impossible for any lactation cookie to affect human milk production," he continues. "This study does suggest that the cookies we studied—under the conditions we studied them—have no discernible effect. The burden of proof seems to now be on those who claim there is an effect."

The study followed 176 U.S. parents who were exclusively breastfeeding healthy two-month-old babies. One group of parents was provided a serving of commercially available lactation cookies to consume daily for a month; the other group of parents ate a serving of conventional cookies not designed to increase lactation, each day for a month. Through a weekly survey, parents reported the quantity of milk they produced after following a validated milk expression protocol using a hospital-grade breast pump, providing data that were analyzed by both the study authors and an independent statistician. These data demonstrated that the impact of consuming lactation cookies did not have a significant effect on how much milk was actually produced or perceived to be produced by the lactating parents.

The authors assert that consumers should be cautious when considering the potential effect of this product, or any food and/or supplement that promotes health-promoting benefits without published, peer-reviewed scientific evidence to support its claims. As the researchers noted, these lactation cookies can contain substantial calories and sugars, which could affect postpartum weight loss efforts and related health issues.

"Despite being a physician and nutrition scientist focused on early-life , I still remember how difficult breastfeeding was for me with both of my children," said study lead author Ana M. Palacios, MD, Ph.D., assistant professor, Department of Health Policy and Community Health, Jiann-Ping Hsu College of Public Health at Georgia Southern University.

"Our research highlights that lactation cookies, which include added sugars and saturated fat, may not have the said purported benefits of increasing milk production. Purchasing  cookies to increase milk production may pose an unnecessary cost and may have additional implications for parents, such as limiting post-pregnancy weight loss and reducing consumption of healthier foods. More research is needed to better understand what foods and nutrients can best help increase  supply in diverse populations."

More information: Ana M. Palacios et al, Effectiveness of lactation cookies on human milk production rates: a randomized controlled trial, The American Journal of Clinical Nutrition (2023). DOI: 10.1016/j.ajcnut.2023.03.010


https://medicalxpress.com/news/2023-04-effectiveness-lactation-cookies-human-production.html

How cells control developmental timetables

 TERESA RAYON HTTPS://ORCID.ORG/0000-0001-5173-1442 Authors Info & Affiliations

Abstract

An overview on the molecular and metabolic mechanisms behind individual cell differences in developmental timing in the segmentation clock and the central nervous system.
From the cell cycle to circadian rhythms, biology relies on precise timing. This includes the duration of a process, the order and direction of events, and the rate at which a process operates. Timing can depend on extrinsic mechanisms that guide the synchronous progression through development of a group of cells via systemic cues. However, timing also relies on intrinsic mechanisms that keep track of time within cells. A focus on developmental timing is gaining momentum, as researchers tease out the molecular and metabolic mechanisms responsible for it.
In evolutionary developmental biology, differences in genetically controlled temporal programs are well recognized and referred to as heterochronies. These include differences in the time of initiation, duration, or rate of a process in comparison with an organisms’ ancestors or other species. Whereas shifts in the time of initiation or duration have been linked to genetic variation of regulatory sequences or differential expression dynamics (12), other heterochronies that emerge from changes in the rate of a process are distinct and usually involve the same genetic program operating at different speeds. This has been termed allochrony and does not seem to be explained by variations in regulatory sequences (Fig. 1, A to C) (34). However, less is known about the mechanisms driving allochronies. ...

Boost in learning by removing nuclear phosphodiesterases and enhancing nuclear cAMP signaling

 VSEVOLOD V. GUREVICH HTTPS://ORCID.ORG/0000-0002-3950-5351 AND EUGENIA V. GUREVICH HTTPS://ORCID.ORG/0000-0002-0563-8295Authors Info & Affiliations

Abstract

cAMP signaling in the nucleus leads to the expression of immediate early genes in neurons and learning and memory. In this issue of Science Signaling, Martinez et al. found that activation of the β2-adrenergic receptor enhances nuclear cAMP signaling that supports learning and memory in mice by removing the phosphodiesterase PDE4D5 from the nucleus through arrestin3 bound to the internalized receptor.

Neuroimmune interactions in the skin can shape the functions of dendritic cells

 BARBARA U. SCHRAML Authors Info & Affiliations

Abstract

Efficient host defense relies on the ability to mount context-dependent immune responses. Dendritic cells (DCs) sense pathogens and tissue damage and subsequently migrate to lymph nodes to present antigens to naive T cells. Through the production of cytokines, DCs further instruct other immune cells about which type of immune response is needed (1). For example, DC-derived interleukin-23 (IL-23) in the skin promotes efficient defense against Candida albicans and Staphylococcus aureus infections, but it also drives psoriasislike skin inflammation (23). Nociceptors are somatosensory neurons that innervate barrier organs and detect noxious stimuli, including mechanical injury, reactive chemicals, inflammatory mediators, and pathogens (4). Nociceptors relay noxious stimuli to the brain as pain or itching sensation and release neuropeptides, which can influence immune cells (4). On page 1315 of this issue, Hanč et al. (5) report the identification of multiple mechanisms by which nociceptors can regulate DCs in the skin.

Effective immunotherapy occurs in neurons

 REBECCA M. NISBET Authors Info & Affiliations

Abstract

The main pathological hallmark of a group of neurodegenerative diseases called tauopathies is the formation of intracellular aggregates composed of the tau protein in the brain. Despite promising results in preclinical studies, tau immunotherapies in clinical development for the treatment of tauopathies, including Alzheimer’s disease, have thus far failed to improve patient cognition. Owing to its critical pathological role, most still argue that tau is an excellent therapeutic target. Therefore, better understanding of the mechanisms by which tau antibodies can remove pathogenic tau from the brain and how these processes can be exploited is paramount for the design of second-generation immunotherapies. On page 1336 of this issue, Mukadam et al. (1) show that the cytoplasmic antibody receptor and E3 ubiquitin ligase tripartite motif-containing 21 (TRIM21) is required for effective tau immunotherapy in a tauopathy mouse model, providing an area of focus for the development of future tau antibodies.

The link between obesity and autoimmunity

 Compelling epidemiological evidence reveals a strong association between being overweight or obese and the risk of developing autoimmune diseases (1). From an immunological standpoint, the cellular and molecular mechanisms linked to this association include the overstimulation of T lymphocytes by nutrient- and energy-sensing pathways. The immunometabolic state of an individual is central to the modulation of immunological self-tolerance that suppresses self-reactivity to avoid autoimmunity. Adipose tissue is an immunologically active organ that influences systemic immune responses through the production of adipocytokines, and, in turn, immune cells affect adipocyte homeostasis and metabolism through the production of pro- and anti-inflammatory cytokines (2). This implies that metabolic overload from obesity can affect immunometabolism, which can alter susceptibility to autoimmune diseases.

Immunological adaptations occur in response to nutritional status: Undernutrition impairs immunity, causing inefficient responses to infections and vaccinations. Conversely, overnutrition favors chronic activation of both innate and adaptive immune cells, with subsequent (low-grade) systemic inflammation. These phenomena occur through the engagement of intracellular nutrient- and energy-sensing pathways and the NACHT, LRR and PYD domains–containing protein 3 (NLRP3) inflammasome, which is a sensor of metabolic stress that is induced by an excess of glucose and lipids, especially in macrophages (23).
Obesity is a risk factor for autoimmune conditions such as type 1 diabetes (T1D) and multiple sclerosis (MS) (45). Environmental and lifestyle factors that increase MS risk include smoking, sun exposure, low vitamin D, Epstein-Barr virus infection, and high body mass index (BMI). Prospective longitudinal studies in young obese individuals found a 1.6- to 1.9-fold increase in the risk of developing MS during adolescence and young adulthood (but not at the time of MS onset); this association with obesity was also confirmed in carriers of the human leukocyte antigen (HLA)–DRB1*15:01 susceptibility allele that is responsible for the presentation of myelin self-antigens to autoreactive T cells (5). Similarly, higher BMI at birth is associated with higher T1D susceptibility in children. Indeed, the incidence of T1D increased almost linearly with a higher birth weight (1.7% increase in incidence per 100-g increase in birth weight) (4).
Mechanistically, it has been suggested that increased body adiposity promotes the hyperactivation of intracellular nutrient- and energy-sensing pathways [such as mechanistic target of rapamycin (mTOR)] with subsequent metabolic overload in peripheral tissues, including resident immune cells that are involved in both effector and regulatory immune responses (6). For example, in obese naïve-to-treatment MS patients, the adipocytokine leptin (secreted in proportion to BMI to inhibit food intake), together with elevated amounts of circulating nutrients, was found to boost inflammatory immune responses. High levels of leptin and nutrients cause constitutive overactivation of mTOR in T cells, with subsequent dysregulated T cell receptor (TCR)–mediated signaling. Overactive mTOR in T cells mimics a strong, supra-physiological TCR stimulation that is not permissive for transcription of the forkhead-box P3 (FOXP3) gene, the expression of which is pivotal for the induction and maintenance of anti-inflammatory CD4+CD25+FOXP3+ regulatory T cells (Tregs) (26). Through leptin overproduction, obesity impairs the proliferation of anti-inflammatory thymic Tregs and their peripheral differentiation from CD4+CD25 conventional T (Tconv) cell precursors (7). Obesity also promotes conversion of Tconv cells into pathogenic inflammatory T helper 1 (TH1) and TH17 cells, thus increasing the risk of altered immunological self-tolerance (see the figure).
Overall, nutrient- and leptin-induced mTOR overactivation inhibits peripheral Treg proliferation and suppressive function and enhances obesity-associated TH1 and TH17 cell differentiation, with a higher risk of MS-associated myelin damage (27). Further, a recent report demonstrated that obese mice converted the classical TH2-predominant immune responses of atopic dermatitis into a severe disease predominantly characterized by TH17-driven inflammation that was caused by reduced activity of the peroxisome proliferator-activated receptor-γ (PPAR-γ) transcription factor (8). The expression of PPAR-− in adipose tissue was also necessary for the development and function of adipose-tissue resident Tregs, suggesting a further bidirectional link between adipose tissue biology and immune tolerance that involves Tregs (27).
Physiological nutrients and leptin fluctuations due to daily cycles of fasting and feeding determine oscillations in mTOR activity that are lost in obesity because of excessive food intake. Therefore, in individuals with a normal BMI and physiological cycles of feeding and fasting, the maintenance and perpetuation of self-tolerance are associated with oscillations of mTOR activity in Tregs. This appears to be necessary for Treg expansion and function in sufficient numbers to suppress pathogenic TH1 and TH17 cells and thus autoimmunity (267).
Of note, mTOR represents a key intracellular node at the crossroad of amino acid, glucose, and lipid metabolism. Furthermore, growth factors linked to nutrition and metabolism, such as leptin, insulin, and insulin-like growth factor 1 (IGF-1), activate mTOR signaling in immune cells, which affects systemic and intracellular immunometabolism and thus inflammation and autoimmunity (26). Adipose tissue also secretes inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor–α (TNF-α), IL-6, IL-17, and interferon-γ (IFN-γ), as well as leptin, which leads to a higher susceptibility to peripheral tissue damage and autoimmunity. Therefore, I propose that metabolic workload—induced by nutrients, adipocyte-derived growth factors, and adipocytokines—may represent an accelerator of autoimmune disorders in people who typically consume an obesogenic Western diet.
It has been demonstrated in mice and in humans that adaptive and innate immune cells can directly influence the pathophysiological events that lead to obesity and obesity-associated metabolic abnormalities (2). This could also contribute to the reduction in Treg numbers observed in obese people. There is an anatomical and functional cross-talk between adipose tissue and the immune system. Indeed, both primary lymphoid organs (bone marrow and thymus) and secondary lymphoid organs (lymph nodes) are generally embedded in and surrounded by adipose tissue. This contiguity allows T cells, Tregs, B cells, dendritic cells, and macrophages to home to adipose tissue. Additionally, adipocytes can express immune-like behaviors (2). For example, adipocytes can clear intracellular bacteria using the same nuclear-binding oligomerization domain 1 (NOD1) pathogen-sensing system of innate immune cells (9). Changes in Treg numbers and function observed in obesity may also affect susceptibility to infections and cancer (2). Indeed, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with the production of autoantibodies and is more severe in obese individuals (10). Additionally, cancer immunotherapy responses are better in obese people than in patients with a lower BMI (2).
GRAPHIC: A. FISHER/SCIENCE
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Polygenic obesity (predisposition to obesity caused by multiple genetic variants and environmental factors) has also been proposed to be an autoimmune-like disease, whereby T cells respond to unknown adipocyte antigens and trigger subsequent uncontrolled food intake, although the mechanism remains to be fully elucidated (11). It is notable that CD4+ T cells isolated from obese mice could transfer an “obesity memory” by promoting weight gain when injected into normal-weight, immune-deficient recipients (11). Thus, it appears that obesity associates with a higher susceptibility to develop autoimmunity not only because adipose tissue boosts autoinflammatory responses but also because obesity itself has autoimmune-like features.
A promising possibility is the manipulation of immune tolerance and autoimmunity through immunometabolic interventions: reduced food and/or calorie intake. Although the idea that fasting could modulate immune responses and alleviate symptoms of autoimmune diseases had mostly been dismissed, studies over the past 20 years have provided evidence that supports the therapeutic potential of behavioral changes and nutritional strategies such as diet, caloric restriction (CR), and different fasting regimens (212). Mild CR, intermittent fasting, and a ketogenic diet have each shown beneficial effects in mouse models of autoimmunity, including experimental autoimmune encephalomyelitis (EAE), experimental rheumatoid arthritis, and experimental colitis (212). I suggest that “starving” pathogenic inflammatory TH1 and TH17 cells could lead to better control of local and systemic inflammation. Similarly, CR allows expansion of Tregs in mice and humans by promoting their generation, proliferation, and function, thereby controlling autoimmunity (2712).
Because adherence to dietary changes is not always possible, a proposed alternative approach is “pseudo-starvation,” whereby drugs that regulate immunometabolism mimic fasting (13). A prototypical example is the mTOR inhibitor rapamycin. Additionally, metformin, an activator of AMP-activated protein kinase (AMPK) that is used to treat type 2 diabetes and overweight individuals, not only controls glucose tolerance but also has anti-inflammatory actions through AMPK-mediated mTOR inhibition (13). Metformin attenuated EAE induction by restricting the infiltration of mononuclear cells into the central nervous system (CNS) and down-regulating the expression of inflammatory cytokines, inducible NO synthase, cell-adhesion molecules, matrix metalloproteinase-9, and chemokines in TH17 cells (14). These effects were also observed in a study of MS patients with metabolic syndrome (15).
First-line drug treatments for MS (either IFN-β or glatiramer acetate) in combination with metformin provided a statistically significant improvement of disease and reduced CNS lesions. These effects were associated with lowered circulating leptin and TH1 and TH17 inflammatory cytokines and increased numbers of peripheral Tregs (15). Similarly, pioglitazone, an activator of PPAR-γ with antidiabetic effects, also provided a metabolic signal of pseudo-starvation to immune cells from treated MS patients by increasing insulin sensitivity and reducing circulating glucose and leptin levels (15). In EAE, pioglitazone treatment controlled the disease course with reduced CNS infiltrates and decreased inflammatory cytokine production and TH1 and TH17 differentiation (15). Also, it is interesting to note that classical anti-inflammatory and immunosuppressive drugs such as salicylate and methotrexate can convey metabolic signals of pseudo-starvation to immune cells through the activation of AMPK (13), along with their classical mechanisms of action. Overall, conferring metabolic signals of pseudo-starvation could be valuable in down-regulating autoinflammatory responses.
It is remarkable that during CR, T cells reprogram their transcriptional signature toward anti-inflammatory properties that limit tissue damage and prolong life span in mice and humans (712). Also, CR induces extensive adaptations in the gut microbiota toward the production of anti-inflammatory metabolites that affect local and systemic immunometabolism (12). Molecules that interact with adipocyte-derived leptin can modulate immune function in various ways depending on metabolic status. For example, neuroendocrine mediators with appetite-stimulating activity such as ghrelin and neuropeptide Y have opposite effects from those of leptin, not only on satiety but also on the peripheral immune responses because they block the secretion of TH1 and TH17 cytokines and suppress EAE (2). Remaining areas for study include the molecular dissection of how single nutrients (i.e., lipids, carbohydrates, and proteins) affect immunological self-tolerance and the temporal window in which CR is an effective therapeutic regimen for obesity-associated autoimmunity.

Acknowledgments

G.M. thanks P. de Candia and A. La Cava for critically reading the manuscript and S. Bruzzaniti for assistance with the figure. G.M. is funded by Fondazione Italiana Sclerosi Multipla (FISM grant 2018/S/5), Progetti di Rilevante Interesse Nazionale (PRIN grant 2017 K55HLC 001), Ministero della Salute (grant RF-2019-12371111), and Ministero dell’Università e Ricerca (INF-ACT grant PE00000007). This work is dedicated to the memory of S. Zappacosta and E. Papa.