Lasting Effects Research Articles

Abstract PO4-23-06: Outcomes and experiences of women denied immediate breast REconstruction after maSTectOmy for bREast cancer during the COVID-19 pandemic - The RESTORE C19 Study

Abstract Introduction 40% of women diagnosed with breast cancer in the UK each year undergo mastectomy and immediate breast reconstruction (IBR) is routinely offered to improve quality of life. During COVID19, this offer was withdrawn to prioritise frontline and emergency services. The RESTORE C19 study aimed to use mixed methods to explore the outcomes, lived experiences and views of women denied IBR during the pandemic. Methods Women not offered IBR between March & October 2020, were identified via B-Map-C, a UK prospective multicentre cohort study documenting changes in breast cancer treatment decisions during the pandemic. All patients were followed up between December 2021 & July 2022 (21-28 months following mastectomy) to explore their ongoing management including whether they had undergone, were awaiting, or had decided against delayed breast reconstruction (DBR) and the procedures performed. Descriptive statistics were used to summarise results. Semi-structured qualitative interviews were undertaken to explore the experiences of this group in more depth. Women were purposively sampled based on treatment centre, age, decision regarding DBR, and procedure performed. A topic guide was developed to explore experiences of breast cancer care; feelings about not having been offered IBR and factors influencing subsequent surgical decision-making. Interviews were transcribed in full and analysed thematically, with data collection and analysis undertaken concurrently and iteratively until saturation was achieved. Full ethical approval was obtained: IRAS 302580, Wales REC 4 21/WA/0347. Results Some 366 women were identified as not having been offered IBR in the B-MaP-C study for whom follow up data was available for 311 (85.0%) from 55 centres. The median age was 50 (range 27-83 years). Most women presented with symptomatic breast cancer (n=239, 76.8%), were fit with no significant comorbidities, had T1 or 2 tumours (n=215, 69.1%) and were node negative (n=186, 59.6%). Almost a fifth (n=58, 18.6%) of women had decided against breast reconstruction completely. Of the remainder, just under 60% (n=149/253), had attended a surgical consultation to discuss DBR and only a third (n=91/253, 36%) had been referred to plastic surgical services to discuss autologous procedures. Only 21 women (6.8%) had received DBR; (16 free flaps, 4 implants, 1 pedicled flap+/-implant). Interviews were performed with 18 women from 5 centres with a median age of 49 years (range 34-67): n=5 women had either received/were awaiting DBR; n=4 had undergone/were awaiting contralateral symmetrising mastectomy and n=9 had decided against/were undecided about further surgery. Whilst all women reported feeling ‘grateful’ for their breast cancer treatment, some felt ‘abandoned’ by healthcare professionals, others that they needed to chase breast surgical teams for care, advice, and support. Partners were also impacted by their experiences with some women describing lasting effects on their relationships. Many women described how their desire for symmetry, either by breast reconstruction or symmetrising mastectomy, had “paled into insignificance” in the months and years following treatment. Conclusions The impact of COVID19 continues to be felt by women treated for breast cancer in the UK. Most women not offered IBR are either still awaiting DBR almost three years after their initial mastectomy or have decided against further surgery. The interviews highlight the trauma many women experienced receiving breast cancer treatment during the pandemic and ongoing issues that, for some, are yet to be fully addressed. There is a need for individualised support to provide women with equitable and timely access to DBR and/or symmetrising mastectomy depending on patient preference to help them move on with their lives. Citation Format: Katherine Fairhurst, Rajiv Dave, Baek Kim, Rachel O'Connell, Raghavan Vidya, P.G. Roy, Stuart McIntosh, Patricia Fairbrother, Jo Skillman, Leila Rooshenas, Shelley Potter. Outcomes and experiences of women denied immediate breast REconstruction after maSTectOmy for bREast cancer during the COVID-19 pandemic - The RESTORE C19 Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-23-06.

Understanding the meaning of the lived experience “maternal role” in women with multiple sclerosis and planning a supportive program: a combined exploratory study protocol

BackgroundThe maternal role is one of the most challenging yet rewarding roles that women experience in their lives. It begins when a woman becomes pregnant, and as the pregnancy progresses, she prepares to fulfill her role as a mother. A woman's health plays a crucial role in her ability to fulfill the maternal role. Multiple sclerosis (MS), as an autoimmune disease, presents unique challenges in achieving this role. Failing to fulfill the maternal role can have lasting consequences for both the mother and the baby. Given the increasing number of women with MS of reproductive age in Iran and the absence of specific programs for this group during pregnancy and postpartum, researchers have decided to develop a supportive program by exploring the meaning of the maternal role and identifying the needs of these women during this period.Methods/materialsThis study will be conducted in 3 stages. The first stage involves a qualitative study to explore the meaning of the "maternal role" in women with MS through a descriptive and interpretive phenomenological approach based on Van Manen's method. Data will be collected through semi-structured interviews with pregnant women with MS and mothers with MS who have children under one-year-old, recruited from the Multiple Sclerosis Society of Mashhad, Iran. The second stage will involve designing a support program based on the findings of the phenomenological study, literature review, and exploratory interviews. A logical model will guide the development of the program, and validation will be conducted using the nominal group technique.DiscussionThis study is the first of its kind in Iran to explore the meaning of the maternal role and develop a support program for women with MS. It is hoped that the results of this study will help address the challenges of motherhood faced by these women.

Use of mindfulness training to improve BAC self-estimation during a drinking episode.

Individuals are often inaccurate at estimating levels of intoxication following doses of alcohol. Previous research has shown that when required to estimate (BAC) at different time points, participants often underestimate their BACs and amounts of alcohol consumed. The present study aimed to increase drinkers' BAC estimation accuracy after drinking alcohol using mindfulness-based feedback to increase their awareness of the interoceptive cues associated with alcohol intoxication. Thirty-three adults were given 0.65 g/kg of alcohol and received one of three training conditions: BAC feedback only, body scan exercise + BAC feedback and no treatment control. Those in the BAC feedback group received feedback concerning their observed BAC during dose exposure. Participants in the body scan group received BAC feedback and underwent a mindfulness exercise to enhance their perception of the acute subjective effects of alcohol. The control group received no BAC estimation training. Participants attended four study sessions: Two training sessions where participants underwent structured training based on their condition and two retention sessions to test for the lasting effects of the training exercises. Retention tests showed that participants in both treatment groups were most accurate in estimating their BACs. There were no differences among the groups in their perceived levels of intoxication at posttraining. The findings suggest that BAC feedback, alone and in combination with, mindfulness training can improve accuracy in estimating BACs. The findings provide preliminary support for the efficacy of mindfulness training in combination with BAC feedback to improve BAC estimation accuracy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The effects of repeat mild traumatic brain injuries on choroid plexus endothelial cells in-vitro

Chronic Traumatic Encephalitis (CTE) is a degenerative brain disorder seen in college and professional football players, and those that play other contact sports like hockey and soccer. It is characterized by a dementia-like phenotype and declination in memory, executive dysfunction, and mood and is associated with repetitive head trauma, as seen in those contact sports. Even with rule changes to protect the players, it is predicted that, on average, college football players experience 1,400-1,500 head impact exposures per year, or roughly 14 per game (Crisco et al., 2010). This is significant because existing literature provides evidence that it is the accumulation of repetitive head trauma, even mild, that eventually leads to lasting and irreparable damage seen in CTE. This study sought to characterize cytokine signaling in repeat mild traumatic brain injuries (rTBI) in choroid plexus endothelial cells (CPECs), the endothelial barrier of the blood-CSF barrier (BCSFB). We hypothesized that regulatory and pro-inflammatory cytokines and chemokines play a role in exacerbating post-rTBI symptomology even days after initial injury. Identifying key cytokines and their respective timepoints post-injury is important to allow us to better treat TBIs, while also preventing subsequent damage that might progress to CTE. To study this hypothesis, primary human CPECs were subjected to a 12% repetitive mechanical elongation strain using the FlexCell Tension system to mimic mild axonal stretching injury. The elongation mechanical strain was repeated 14 times over a 1-hour period, which is roughly the average number of impacts experienced by players during a one-hour college football game. We collected supernatant over 24-, 48-, 72-, and 96-hours post-injury and examined 36 different cytokines using RND microarrays following manufacturer’s instructions. Controls included cells subjected to no mechanical strain and cells that only received one total mechanical strain. Several notable cytokines and chemokines were altered during this period, including RANTES (CCL5), CXCL12, and macrophage migration inhibitory factor (MIF). RANTES is highly correlated with Alzheimer’s disease, a neurodegenerative disease and CTE relative, and CXCL12 and MIF are highly correlated with inflammatory processes. Many cytokine changes were more pronounced in the period between 24- and 48-hours after injury. However, there were lasting changes compared to the controls up to 96-hours later. These findings can be used to begin to understand the complexity of human CPEC cytokine signaling at the BCSFB when these cells react to the strain forces of repeat mild TBIs like those seen in college football players. This also gives us further insight into the lasting effects of rTBIs and the possible relation to CTE. With these results in mind, we plan to continue to monitor cytokines and chemokines up to two weeks post injury to determine if, and when, cytokine values return to baseline values post-injury. This project was funded by a Senior Research Grant from the Indiana Academy of Science and from a Faculty Research Development Grant from Marian University College of Osteopathic Medicine. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Parapelvic Renal Cyst Treatment with Flexible Ureteroscopy: Single Centre Experience.

This study aimed to assess the feasibility, safety, and efficacy of an endoscopic parapelvic renal cyst (PRC) incision using flexible ureterorenoscopy (fURS). We retrospectively reviewed data concerning 16 patients in whom PRC incisions had been performed using fURS between January 2016 and January 2022. Two patients were excluded from the study owing to a lack of follow-up information. The cysts of all the patients were evaluated preoperatively by computed tomography. The patients' age, gender, cyst size, presenting symptoms, postoperative complications, and pre- and post-treatment visual analogue scale (VAS) scores were evaluated. Surgical success was defined as a reduction of more than half of the cyst size in the sixth postoperative month. A total of 14 patients were included in this study. The patients' mean age was 52.6 ± 8.8 years, and the mean cyst size was 69.1 ± 15.5 mm. Twelve (85.7%) patients presented with flank pain. Clavien-Dindo grade 1 complications were observed in two patients (14.3%), and grade 2 complications were observed in one (7.1%). The median VAS scores were significantly lower after treatment than before in patients who presented with flank pain (2 (1-2.8) vs 8 (7-8), respectively; p = 0.002). Surgical success rate was detected in 11 patients (78.6%) six months after the treatment. Endoscopic incision of the PRC is a feasible treatment modality with high success rates and low complication rates. However, multicentre studies with larger populations and longer follow-ups are needed to evaluate the lasting effects.

Primary Infection and Supernatants Generated by Pseudomonas aeruginosa ExoY Have Lasting Effects on Cyclic Nucleotide Signaling in Pulmonary Endothelial Cells

Rationale: Pseudomonas aeruginosa is an opportunistic pathogen and a common cause of hospital-acquire pneumonia. This gram-negative bacterium has an arsenal of virulence factors including the type three secretion system (TTSS), which encodes for an injection type needle and exotoxins. One of the four exotoxins, ExoY, is a promiscuous nucleotidylyl cyclase that utilizes F-actin as a cofactor to generate both canonical and non-canonical cyclic nucleotides (cAMP, cGMP and cCMP and cUMP respectively). While it is well known that activation of endogenous adenylyl and guanylyl cyclase leads to intracellular increases in cAMP and cGMP and release into the extracellular space, whether ExoY generated cyclic nucleotides are also effluxed out of the cell into the extracellular space is not known. In addition, it is unclear whether presence of the bacteria themselves affects endogenous cAMP signaling. Further, infection with P. aeruginosa expressing ExoY generates virulent cytotoxic amyloids from lung endothelium; however, whether these cytotoxic amyloids disrupt agonist-induced endogenous cAMP generation is unknown. Thus, we tested the hypothesis that during primary infection, cAMP and cGMP are effluxed into the extracellular space, while the primary infection itself and sterile supernatants from the primary infection attenuate isoproterenol induce increases in cAMP in pulmonary microvascular endothelial cells (PMVECs). Methods: During primary infection, PMVECs were inoculated with PBS (vehicle control) or 3 different strains of P. aeruginosa at an moi 20:1. Strains ExoY+ and ExoYK81M have a fully functional TTSS and express either catalytically active or inactive ExoY, respectively, while a third strain, ExoYTM, is unable to translocate ExoY into eukaryotic cells. During the last 15 minutes of the 4-hour infection, cells were stimulated with vehicle or isoproterenol (1 μM) and rolipram (10 μM) and cAMP and cGMP measured in the lysate and media. In separate experiments, supernatants from a primary infection were generated using the same three strains of bacteria at moi 20:1 and 4 hours after inoculation, the supernatants collected and sterilized using a 0.2 μm filter. Sterilized supernatants were added to naïve PMVECs and during the last 15 minutes of the 4-hour inoculation, cells stimulated with vehicle or isoproterenol (1 μM) and rolipram (10 μM) and cAMP and cGMP measured in the lysate and media. Results: Cyclic AMP and cGMP were elevated in both the lysate and media of PMVECs following 4-hour infection with ExoY+ and the total isoproterenol and rolipram-stimulated cAMP response was attenuated by the presence of bacteria, ExoYK81M and ExoYTM, and further blunted with ExoY+ infection. Further, inoculation with ExoYK81M and ExoYTM supernatants attenuated the total isoproterenol and rolipram-stimulated cAMP response, which was further blunted by ExoY+ supernatants. Conclusions: Overall, we demonstrate PMVECs release a large cAMP and cGMP pool into the extracellular space and both primary infection and supernatants derived from the primary infection attenuate agonist induced elevations in cAMP. HL121513, HL66299. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Thermal stressors during embryo incubation have limited ontogenic carryover effects in brook trout

Winter climate is changing rapidly in northern latitudes, and these temperature events have effects on salmonid thermal biology. Stressors during winter egg incubation could reduce hatching success and physiological performance of fall-spawning fishes. Here we quantified the potential for ontogenic carryover effects from embryonic thermal stress in multiple wild and hatchery-origin populations of brook trout (Salvelinus fontinalis), a temperate ectotherm native to northeastern North America. Fertilized eggs from four populations were incubated over the winter in the laboratory in four differing thermal regimes: ambient stream-fed water, chronic warming (+2 °C), ambient with a mid-winter cold-shock, and short-term warming late during embryogenesis (to stimulate an early spring). We examined body size and upper thermal tolerance at the embryonic, fry (10 weeks post-hatch and 27–30 weeks post-hatch) and gravid adult (age 2+) life stages (overall N = 1482). In a separate experiment, we exposed developing embryos to acute seven-day heat stress events immediately following fertilization and at the eyed-egg stage, and then assessed upper thermal tolerance (CTmax) 37 weeks post-hatch. In all cases, fish were raised in common garden conditions after hatch (i.e., same temperatures). Our thermal treatments during incubation had effects that varied by life stage, with incubation temperature and life stage both affecting body size and thermal tolerance. Embryos incubated in warmer treatment groups had higher thermal tolerance; there was no effect of the mid-winter melt event on embryo CTmax. Ten weeks after hatch, fry from the ambient and cold-shock treatment groups had higher and less variable thermal tolerance than did the warmer treatment groups. At 27–30 post-hatch and beyond, differences in thermal tolerance among treatment groups were negligible. Collectively, our study suggests that brook trout only exhibit short-term carryover effects from thermal stressors during embryo incubation, with no lasting effects on phenotype beyond the first few months after hatch.

Nandrolone treatment of adolescent female rats alters reproductive tissue and gonadal steroid profile

Anabolic androgenic steroids (AAS) are drugs that mimic the chemical structure of testosterone. The most commonly AAS used by young adults is nandrolone. In the USA, more than 20 % of AAS users started using steroids before the age of 20. This is alarming as most female users are unaware of the detrimental reproductive effects of AAS use such as amenorrhea, anovulation and clitoromegaly. An additional detrimental effect of AAS is their addictive liability. Previous studies indicate that animals self-administer AAS. Furthermore, AAS can cross-sensitize with other drugs of abuse such as cocaine. Our goal was to elucidate the effects of both AAS and cocaine in the reproductive system of female rats. Our hypothesis is that AAS will have a detrimental effect on the reproductive system of female rats. Adolescent female rats were divided into two large groups, one that received nandrolone decanoate (20mg/kg/sc) and another that received sesame oil (vehicle) for 10 successive days starting on day 28. Animals were further subdivided into groups that received saline or cocaine injections (0.01cc/10g) for a total of 4 groups: Oil-Saline, ND-Saline, Oil-Cocaine and ND-Cocaine. One cohort (Day 40) received cocaine or saline injections (0.01cc/10g) from days 40 to 44 and on days 52 and day 62. The other cohort (Day 65) received cocaine or saline injections from days 65 to 69 and on days 77 and 87. Our data show that administration of nandrolone during adolescence increased body weight of female rats. Ovarian weight was decreased, and ovarian tissue presented multiple cysts with fewer follicles. Nandrolone also disrupted uterine morphology. The uterine lumen was increased, the endometrial thickness reduced and thickness of myometrial tissue, as well as uterine weight, was increased. In addition, nandrolone reduced both endometrial estrogen and androgen receptors, an effect lost by day 88. In contrast, uterine tissue at day 63 showed an increase in progesterone receptor (PR) immunoreactivity, whereas PR immunoreactivity decreased in tissue obtained at Day 88 regardless of whether animals had received cocaine. Cocaine also increased PR receptors in uterine tissue at day 63 and 88. Animals treated with nandrolone had higher serum concentrations of testosterone and estradiol and a lower level of progesterone. These data show that nandrolone when administered in supraphysiologic doses during adolescence, has long lasting effects on the reproductive system of the female rat due to the depot effects and long half-life of this drug. These data warrant further research in this area to determine the long-term consequences of early nandrolone exposure on the female reproductive system, as well as fertility. Financial assistance was provided by the Offce of International Science and Engineering (OISE) of NSF through the Partnerships for Research and Education (PIRE) Program (OISE-#1545803). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Mechanisms Underlying Long-Term Facilitation in the Carotid Body

Glutamate and γ-aminobutyric acid (GABA) are major modulators of excitatory and inhibitory transmission in the mammalian brain. Glutamate transmission is critical for neural plasticity, learning and memory, whereas GABA plays a fundamental role in regulating neuronal excitability and facilitating the generation of neural oscillations. Our data indicates that both glutamate and GABA are released in the carotid body (CB) to modulates its response to hypoxia. Objectives: We set out to investigate whether repeated stimulation with glutamate and GABA induces lasting effects on CB afferent discharge. Hypothesis: We hypothesised that glutamate/GABA mediates long-term facilitation (LTF) of CB afferent activity. Methods: We mined high-throughput RNA sequence data and used immunohistochemistry to map components underlying neuroplasticity in the CB in Wistar and Spontaneously-hypertensive rats (SHR). CSN discharge was measured as a functional readout of CB function from an ex vivo arterially perfused carotid artery-CB preparation. Data: We catalogue the expression of glutamate receptors (R) and transporters in the rat and mouse CB. We found N-methyl-D-aspartic acid receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR) and transporters to be localised to the CB chemosensory cells. Targeted administration of 15 mM glutamate activated the carotid sinus nerve ( p=0.003). Repetitive [5 times, 2-minute duration, 5-minute intervals] application of 15 mM glutamate evoked LTF of CB afferent discharge as demonstrated by both a 12-fold increase in basal firing frequency (0.78 ± 0.37 vs 1232 ± 596 spikes 1s−1; p = 0.004) over 60 minutes ( p = 0.004) and amplification of the evoked response to chemical hypoxia (CN−; 1.23 μmol bolus) by 2-fold ( p = 0.009). The stimulation paradigm was specific as neither application of glutamate, 5 times for 1-minute at 5-minute intervals, nor a single glutamate exposure evoked LTF. In contrast, repeated application of 15mM GABA [3 times for 1-minute at 5-minute intervals] evoked long-term depression (LTD) of CB afferent activity as seen by a reduced basal discharge from 10.5 to 3.5 spikes 1s−1 ( p = 0.0004) and a 2-fold suppression of the response to chemical hypoxia ( p = 3.71 x 10−5). Summary of the data: Repetitive exposure to glutamate using a specific protocol increased basal discharge of CB afferent output akin to LTF and caused sensitisation of evoked responses to CN−. Repeated exposures of GABA depressed the CB basal discharge akin to LTD. A statement of the conclusions: It is conceivable that processes such as LTP and LTD operate in the CB to modulate the set point of peripheral chemoreceptor sensitivity and its state-dependent tonicity; the role of LTP in peripheral chemoreflex sensitisation in disease remains to be determined. Research was supported by the Health Research Council of New Zealand and the Sidney Taylor Trust. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Evidence-Based Strategies for Injury Prevention and Exercise Prescription in Elderly Communities: The Physical Therapist's Perspective

Injury prevention and exercise prescription are critical components of healthcare for older adults. Physical therapists play a critical role in fall risk screening, assessment, and prevention in elderly communities. By incorporating STEADI (Stopping Elderly Accidents, Deaths, and Injuries) and other evidence-based tools and resources, physical therapists can help identify and address fall risk factors, link older adults with community-based programs and resources, and reduce the incidence of falls and related injuries in this population. Evidence-based interventions for fall prevention include exercise interventions that are tailored and include a combination of exercise types, considering individual abilities and preferences. Exercise programs can reduce falls in older people living in residential aged care facilities, but exercise has little or no lasting effect on falls after the end of a program. Physical therapists should consider the patient's fall risk, functional limitations, and comorbidities when prescribing exercises for balance and falls prevention. Physical therapists can help elderly communities implement evidence-based strategies for injury prevention and exercise prescription by adopting a person-centered approach, challenging ageist stereotypes, using sound outcome measures, prioritizing physical activity, and collaborating with other healthcare professionals. By doing so, physical therapists can promote the health, independence, and well-being of older adults, and help them lead active, fulfilling lives. A combination of strength, balance, and functional training exercises, as well as other evidence-based strategies, can significantly reduce the risk of falls in elderly communities. Physical therapists and healthcare providers should consider these interventions when developing fall prevention programs for older adults. Exercise interventions for preventing falls in elderly communities should be implemented regularly, with a frequency of at least three sessions per week, and for a duration of up to 12 months. Keywords: Elderly communities, injury prevention, exercise prescription in elderly, falls prevention, aging

Pre-Weaning Overfeeding Promotes Prepubertal Obesity and Evokes Sexual Dysfunction in Young Adult Rats

Obesity in early life can contribute to several health issues in adulthood, including diabetes, high blood pressure, and high cholesterol, and these conditions are associated with sexual dysfunction. Here, we hypothesized that pre-weaning overfeeding can have long lasting effects on body fat distribution and erectile function that will be observed in young adult males. On postnatal day (PND 1), Wistar rats were separated into two groups: normal litter (NL) with 10 pups per dam, or small litter (SL) with 3 pups per dam. Male rats (n = 8-10 per group) were then assessed at two different time points: during the prepubertal stage (PND 40) and in adulthood (PND 120). Erectile function was assessed only after sexual maturation (i.e., PND 120). Body weight, retroperitoneal and perigonadal adipose tissue (fat pad weight/100g of the body) were evaluated. Following euthanasia at PND 120, the corpus cavernosum (CC) was removed to perform functional studies using a strip myograph. Contractile and relaxation responses were evaluated by electrical field stimulation (EFS) and concentration-response curves (CRC) to phenylephrine [Phe, 1nM-30μM, millinewton (mN)] or acetylcholine (Ach 1nM-30μM, % relaxation) were performed. At the prepubertal stage, SL rats had higher body weight (NL 149±3 vs. SL 186±5, g, p<0.05), and increased retroperitoneal (NL 0.17±0.01 vs. SL 0.32±0.03, g/100g, p<0.05) and perigonadal (NL 0.38± 0.02 vs. SL 0.45±0.03, g/100g, p<0.05) adipose tissue. At PND 120, SL group presented increased body weight (NL 534.2.7±13 vs. SL 631.6±10, g, p<0.05), retroperitoneal (NL 1.31±0.11 vs. SL 1.82±0.14, g/100g, p<0.05) and perigonadal (NL 1.74±0.10 vs. SL 2.18±0.15, g/100g, p<0.05) adipose tissue when compared with NL group. The CC of SL rats at PND 120 had increased contraction induced by EFS for all frequencies (1 Hz: NL 0.5 ± 0.2 mN vs. SL 0.9 ± 0.2 mN; 4 Hz: NL 1.2 ± 0.3 mN vs. SL 1.8 ± 0.2 mN; 16 Hz: NL 1.9 ± 0.4 mN vs. SL 3 ± 0.4 mN), whereas the relaxation was decreased in SL (1 Hz: NL 0.77 ± 0.18% vs. SL 0.27 ± 0.09%; 4 Hz: NL 2.48 ± 0.26% vs. SL 1.36 ± 0.41%; 16 Hz: NL 3.06 ± 0.28% vs. SL 2.39 ± 0.53%). CRC showed increased contractile response to Phe (Emax NL 2.3±0.3 vs. SL 3.8± 0.6, mN, p=0.05) and reduced potency of ACh (pEC50 NL 6.4±0.6 vs. SL 4.9±0.7, mN, p=0.1) in the CC of SL. Incubation with indomethacin (10μM) abolished the differences in the contractile response induced by EFS or Phe between SL and NL, suggesting a heightened inflammatory response. Moreover, the CC of SL rats presented increased expression of Phospho-p44/42 MAPK (NL 0.9±0.25 vs. SL 1.3±0.11, p=0.2). Finally, proteome profiler cytokine array of serum samples from SL animals showed increased circulating levels of cytokines and chemokines associated with obesity, aging, and vascular dysfunction. Together, these data suggest that early prepubertal obesity has long-lasting negative implications on sexual function in young adulthood. National Institutes of Health (NIH); American Heart Association (AHA); Fulbright Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A novel reverse perilesional home phototherapy can promote the repigmentation of vitiligo patches with complete leukotrichia: A 12-week, open-label, double-arm, multicenter, randomized clinical trial.

Existing phototherapies are ineffective for treating patients with vitiligo with complete leukotrichia. We compared the efficacy of reverse perilesional irradiation, during which only the lesional areas are covered, with conventional narrowband ultraviolet B (NB-UVB) home phototherapy for repigmentation of non-segmental vitiligo in patients with complete leukotrichia. This was a 12-week, open-label, double-arm, multicenter clinical trial, with a total of 121 patients with non-segmental vitiligo who were randomly divided into two groups (both received topical tacrolimus): the conventional NB-UVB irradiation (CI) and reverse perilesional NB-UVB irradiation (RI) groups. A statistically significant difference in improvement from baseline was observed in the RI group compared with the findings in the CI group (-30.8% ± 11.8% vs. -25.5% ± 11.05%, respectively [p = .010]; pair-wise comparison p = .900 at week 4, p = .104 at week 8, and p = .010 at week 12). At week 12, the average percentage change from baseline of leukotrichia in the irradiation area significantly decreased from 100% to 82.2% ± 13.65% in the RI group, and from 100% to 88.7% ± 9.64% in the CI group (p = .027). Adverse events were minor, including desquamation, dryness, erythema, and blisters. No severe or lasting side effects were observed during the study. RI mediated better repigmentation of vitiligo with complete leukotrichia than CI.

Early-life experience and political leaders’ policy preference: Evidence from China’s Zhiqing officials

By exploiting both the unique institutional setting of the Chinese political system and the quasi-experimental features of a massive nationwide rural rustication movement in China during the 1960–1970s, this paper explores the relationship between leaders’ early-life experiences and their policy preferences. Based on a unique panel data set of 318 regional units from 2003 to 2012, we find that those units are associated with more generous rural welfare programs when governed by zhiqing leaders, who experienced rural rustication during their early adulthood. We further find that this association becomes stronger when leaders spent more time in rustication or rusticated in places that were much worse developmentally than their hometowns. These findings remain consistent after applying various robustness checks and accounting for possible selection biases. We interpret these findings as evidence showing that emotional attachment, cognitive sympathy, deservedness justification and self-efficacy accrued through shared life experiences during the sensitive years of adolescence could have lasting effects in configuring leaders’ late policy preferences when they come into power. Our findings lend support to the argument that a leader’s early-life experience provides useful information to predict this leader’s policy styles.

Effects of parental childhood cultural health environment on children’s influenza and COVID-19 vaccination status

Most studies examining factors associated with pediatric influenza (flu) and coronavirus disease (COVID-19) vaccination uptake focus on parental demographics. We examined whether the childhood cultural health environment (CHE) of parents (measured by self-reported regular attendance at doctor and dentist visits during childhood) was associated with flu and COVID-19 vaccination of their children. Using 2023 survey data from 397 US parents and causal inference methods, we estimated the average causal effect of parental CHE on flu vaccination rates (0.16 [95 % confidence interval: 0.06,0.27]) and COVID-19 (0.14 [95 % confidence interval: 0.04,0.24]), indicating that if all parents had attended regular doctor/dentist visits as children, flu and COVID-19 vaccination rates in children would be 16 % and 14 % higher, respectively, than if none had. Our findings suggest that early life exposure to medical and dental care has significant and lasting effects on the health of individuals and families.

Reducing Prejudice toward Refugees: Evidence That Social Networks Influence Attitude Change in Uganda

Interventions aimed at reducing prejudice toward refugees have shown promise in industrialized countries. However, the vast majority of refugees are in developing countries. Moreover, while these interventions focus on individual attitude change, attitudes often do not shift in isolation; people are embedded in rich social networks. We conducted a field experiment in northwestern Uganda (host to over a million refugees) and find that perspective-taking warmed individual attitudes there in the short term. We also find that the treatment effect spills over from treated households to control ones along social ties, that spillovers can be positive or negative depending on the source, and that peoples’ attitudes change based on informal conversations with others in the network after the treatment. The findings show the importance of understanding the social process that can reinforce or unravel individual-level attitude change toward refugees; it appears essential to designing interventions with a lasting effect on attitudes.

The effects of gender-specific local labor demand on birth and later outcomes

We study the effects of local labor market conditions during early pregnancy on birth and later outcomes. Using a longitudinal survey of newborns in Japan, we find that improvements in employment opportunities increase the probability of low birth weight and premature birth. We also examine the effects of gender-specific labor market conditions. An increase in labor demand for women has a large negative effect on gestational age, especially for mothers who gave birth at relatively young ages. However, we find little evidence of a lasting negative effect of an increase in labor demand during early pregnancy on serious health conditions or developmental delays in early childhood. Using prefecture-level panel data, we confirm that the negative effect on infant birth weight is not driven by selective fertility and mortality.

Short-term heat waves have long-term consequences for parents and offspring in stickleback.

Extreme temperature events, such as heat waves, can have lasting effects on the behavior, physiology, and reproductive success of organisms. Here, we examine the impact of short-term exposure to a simulated heat wave on condition, parental care, and reproductive success in a population of threespine stickleback (Gasterosteus aculeatus), a small fish with exclusive paternal care, currently experiencing regular heat waves. Males were either exposed to a simulated heat wave (23 °C) for 5 d or held at an ideal temperature (18 °C). Following this 5-d treatment, all males were transferred to 18 °C, where they completed a full parenting cycle. Offspring were raised at 18 °C. We found that while mass and body condition were unaffected in males exposed to a heat wave, cortisol responses were dampened across the nesting cycle compared to control males. In addition, heat wave males had longer latency for eggs to hatch, lower hatching success, and showed lower levels of parental care behavior compared to control males. Offspring of heat wave males had lower body condition, affecting swimming performance. Altogether, our results highlight the long-term impact that even short-term events can have on reproductive success, parental behavior, and subsequent generations, providing insight into population responses to rapid environmental change.

Adolescents’ Beliefs About Sex: The Moderating Effects of Peer Attitudes

Peer beliefs and attitudes play a prominent role in adolescent behaviors. Various curricula have been developed to teach students about sexual health from a skills-based perspective with successful, lasting effects. This study examined how adolescents’ expectancies for success in and values held for a sexual health curriculum are related to their attitudes toward waiting to have sex, attitudes toward using a condom, self-efficacy in negotiating condom use, self-efficacy in refusal skills, and self-efficacy in navigating tricky situations, depending on their perceptions of their peers’ attitudes. Results indicate that perceived peer attitudes toward waiting to have sex were a significant moderator, more so than peer attitudes about condom use. Additionally, results suggest that sex plays a role in students’ sexual health beliefs and self-efficacies. Future work should examine further explanatory paths and influences such as caregivers.

Effectiveness of a universal, school-based, online programme for the prevention of anxiety, depression, and substance misuse among adolescents in Australia: 72-month outcomes from a cluster-randomised controlled trial

The CSC study found that the universal delivery of a school-based, online programme for the prevention of mental health and substance use disorders among adolescents resulted in improvements in mental health and substance use outcomes at 30-month follow-up. We aimed to compare the long-term effects of four interventions-Climate Schools Combined (CSC) mental health and substance use, Climate Schools Substance Use (CSSU) alone, Climate Schools Mental Health (CSMH) alone, and standard health education-on mental health and substance use outcomes among adolescents at 72-month follow-up into early adulthood. This long-term study followed up adolescents from a multicentre, cluster-randomised trial conducted across three states in Australia (New South Wales, Queensland, and Western Australia) enrolled between Sept 1, 2013, and Feb 28, 2014, for up to 72 months after baseline assessment. Adolescents (aged 18-20 years) from the original CSC study who accepted contact at 30-month follow-up and provided informed consent at 60-month follow-up were eligible. The interventions were delivered in school classrooms through an online delivery format and used a mixture of peer cartoon storyboards and classroom activities that were focused on alcohol, cannabis, anxiety, and depression. Participants took part in two web-based assessments at 60-month and 72-month follow-up. Primary outcomes were alcohol use, cannabis use, anxiety, and depression, measured by self-reported surveys and analysed by intention to treat (ie, in all students who were eligible at baseline). This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000723785), including the extended follow-up study. Of 6386 students enrolled from 71 schools, 1556 (24·4%) were randomly assigned to education as usual, 1739 (27·2%) to CSSU, 1594 (25·0%) to CSMH, and 1497 (23·4%) to CSC. 311 (22·2%) of 1401 participants in the control group, 394 (26·4%) of 1495 in the CSSU group, 477 (37·%) of 1289 in the CSMH group, and 400 (32·5%) of 1232 in the CSC group completed follow-up at 72 months. Adolescents in the CSC group reported slower year-by-year increases in weekly alcohol use (odds ratio 0·78 [95% CI 0·66-0·92]; p=0·0028) and heavy episodic drinking (0·69 [0·58-0·81]; p<0·0001) than did the control group. However, significant baseline differences between groups for drinking outcomes, and no difference in the predicted probability of weekly or heavy episodic drinking between groups were observed at 72 months. Sensitivity analyses increased uncertainty around estimates. No significant long-term differences were observed in relation to alcohol use disorder, cannabis use, cannabis use disorder, anxiety, or depression. No adverse events were reported during the trial. We found some evidence that a universal online programme for the prevention of anxiety, depression, and substance use delivered in early adolescence is effective in reducing the use and harmful use of alcohol into early adulthood. However, confidence in these findings is reduced due to baseline differences, and we did not see a difference in the predicted probability of drinking between groups at 72-month follow-up. These findings suggest that a universal prevention programme in adolescence is not sufficient to have lasting effects on mental health and substance use disorders in the long term. In addition to baseline differences, substantial attrition warrants caution in interpretation and the latter factor highlights the need for future long-term follow-up studies to invest in strategies to increase engagement. Australian National Health and Medical Research Council.

Impact of theta transcranial alternating current stimulation on language production in adult classic galactosemia patients.

Patients with classic galactosemia (CG), an inborn error of galactose metabolism, suffer from impairments in cognition, including language processing. Potential causes are atypical brain oscillations. Recent electroencephalogram (EEG) showed differences in the P300 event-related-potential (ERP) and alterations in the alpha/theta-range during speech planning. This study investigated whether transcranial alternating current stimulation (tACS) at theta-frequency compared to sham can cause a normalization of the ERP post stimulation and improves language performance. Eleven CG patients and fourteen healthy controls participated in two tACS-sessions (theta 6.5 Hz/sham). They were engaged in an active language task, describing animated scenes at three moments, that is, pre/during/post stimulation. Pre and post stimulation, behavior (naming accuracy, voice-onset-times; VOT) and mean-amplitudes of ERP were compared, by means of a P300 time-window analysis and cluster-based-permutation testing during speech planning. The results showed that theta stimulation, not sham, significantly reduced naming error-percentage in patients, not in controls. Theta did not systematically speed up naming beyond a general learning effect, which was larger for the patients. The EEG analysis revealed a significant pre-post stimulation effect (P300/late positivity), in patients and during theta stimulation only. In conclusion, theta-tACS improved accuracy in language performance in CG patients compared to controls and altered the P300 and late positive ERP-amplitude, suggesting a lasting effect on neural oscillation and behavior.