Developmental pathways of the family bereavement program to promote growth 15 years after parental death.

Although parental death increases the risks of negative developmental outcomes, some individuals report personal growth, an outcome that has received little attention. We tested a developmental cascade model of postloss growth in 244 parentally bereaved youth (ages 8-16 at baseline) from 156 families who participated in a randomized controlled trial of a family-based intervention, the Family Bereavement Program (FBP). Using five waves of data, the present study examined the prospective associations between the quality of parenting immediately following the FBP and postloss growth 6 and 15 years later, and whether these associations were mediated by changes in intra- and interpersonal factors (mediators) during the initial 11 months following the FBP. The mediators were selected based on the theoretical and empirical literature on postloss growth in youth. Results showed that improved quality of parenting immediately following the FBP was associated with increased support-seeking behaviors and higher perceived parental warmth at the 11-month follow-up, both of which were related to postloss growth at the 6-year follow-up and 15-year follow-up. No support was found for the other hypothesized mediators that were tested: internalizing problems, intrusive grief thoughts, and coping efficacy. To promote postloss growth for parentally bereaved youth, bereavement services should target parent-child relationships that help youth feel a sense of parental warmth and acceptance and encourage youth to seek parental support. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Preventing Adverse Outcomes for Bereaved Youth: Indirect Effects From a Randomized Trial of the Family Bereavement Program on Fear of Abandonment, Grief, and Mental Health.

OBJECTIVES: We investigated whether the self-system belief of fear of abandonment mediated the effects of intervention-induced change in 2 protective factors-positive parenting and adaptive coping-and one risk factor-stressful events-on youth mental health problems and maladaptive grief. This study extends prior research on fear of abandonment in youth who experience parental death by examining pathways through which a program reduced fear of abandonment and, in turn, affected subsequent pathways to child mental health problems in the context of a randomized experiment. METHODS: This is a secondary data analysis study. We used data from the 4-wave longitudinal 2-arm parallel randomized controlled trial of the Family Bereavement Program conducted between 1996 and 1999 in a large city in the Southwestern United States. The sample consisted of 244 offspring between 8 and 16 at the pretest. They were assessed again at posttest, 11-month follow-up, and 6-year follow-up. Offspring, caregivers, and teachers provided data. RESULTS: Mediation analyses indicated that intervention-induced reductions in stressful events were prospectively associated with a lower fear of abandonment. For girls, fear of abandonment was related to self-reported maladaptive grief and teacher-reported internalizing problems 6 years later. CONCLUSIONS: This study extends prior research on the relation between intervention-induced changes in risk and protective factors and improvements in outcomes of bereaved youth. The findings support the reduction of stressful events as a key proximal target of prevention programs for bereaved children.

Effects of a preventive parenting intervention for bereaved families on the intergenerational transmission of parenting attitudes: Mediating processes.

This study evaluated whether the Family Bereavement Program (FBP), a prevention program for parentally bereaved families, improved parenting attitudes toward parental warmth and physical punishment in young adult offspring 15 years after participation and identified mediational cascade pathways. One hundred fifty-six parents and their 244 offspring participated. Data were collected at pretest (ages 8-16), posttest, and six- and 15-year follow-ups. Ethnicity of offspring was: 67% non-Hispanic Caucasian, 16% Hispanic, 7% African American, 3% Native American, 1% Asian or Pacific Islander, and 6% other; 54% were males. There was a direct effect of the FBP on attitudes toward physical punishment; offspring in the FBP had less favorable attitudes toward physical punishment. There were also indirect effects of the FBP on parenting attitudes. The results supported a cascade effects model in which intervention-induced improvements in parental warmth led to fewer externalizing problems in adolescence/emerging adulthood, which in turn led to less favorable attitudes toward physical punishment. In addition, intervention-induced improvements in parental warmth led to improvements in anxious romantic attachment in mid-to-late adolescence/emerging adulthood, which led to more favorable attitudes toward parental warmth in emerging/young adulthood. These findings suggest that the effects of relatively brief prevention programs may persist into subsequent generations.

Peptides originally derived from Chilobrachys jingzhao tarantula venom possess beneficial effects on pancreatic beta cell health and function.

Clinical approval of the glucagon-like peptide-1 (GLP-1) mimetic exenatide for the treatment of type 2 diabetes highlights the therapeutic effectiveness of venom-derived peptides. In the present study, we examined and characterised the glucose-lowering potential of synthetic Jingzhaotoxin IX and Jingzhaotoxin XI peptides, which were originally isolated from the venom of the Chinese earth tarantula Chilobrachys jingzhao. Following confirmation of lack of beta-cell toxicity of synthetic peptides, assessment of enzymatic stability and effects on in vitro beta-cell function were studied, alongside putative mechanisms. Glucose homeostatic and appetite suppressive actions of Jingzhaotoxin IX and Jingzhaotoxin XI alone, or in combination with exenatide, were then assessed in normal overnight fasted C57BL/6 mice. Synthetic Jingzhaotoxin peptides were non-toxic and exhibited a decrease in mass of 6 Da in Krebs-Ringer bicarbonate buffer suggesting inhibitor cysteine knot (ICK)-like formation, but interestingly were liable to plasma enzyme degradation. The Jingzhaotoxin peptides evoked prominent insulin secretion from BRIN BD11 beta-cells, with activity somewhat characteristic of Kv2.1 channel binding. In addition, Jingzhaotoxin peptides enhanced beta-cell proliferation and provided significant protection against cytokine-induced apoptosis. When injected co-jointly with glucose, the Jingzhaotoxin peptides slightly decreased blood-glucose levels but had no effect on appetite in overnight fasted mice. Whilst the Jingzhaotoxin peptides did not enhance exenatide-induced benefits on glucose homeostasis, they augmented exenatide-mediated suppression of appetite. Taken together, these data highlight the therapeutic potential of tarantula venom-derived peptides, such as Jingzhaotoxin IX and Jingzhaotoxin XI either alone or in combination with exenatide, for diabetes and related obesity.

A novel peptide isolated from Aphonopelma chalcodes tarantula venom with benefits on pancreatic islet function and appetite control.

Proof-of-concept for therapeutic application of venom-derived compounds in diabetes is exemplified by the incretin mimetic, exenatide, originally extracted from the saliva of the venomous Heloderma suspectum lizard. In this regard, we have isolated and sequenced a novel 28 amino acid peptide named Δ-theraphotoxin-Ac1 (Δ-TRTX-AC1) from venom of the Mexican Blond tarantula spider Aphonopelma chalcodes, with potential therapeutic benefits for diabetes. Following confirmation of the structure and safety profile of the synthetic peptide, assessment of enzymatic stability and effects of Δ-TRTX-AC1 on in vitro beta-cell function were studied, alongside potential mechanisms. Glucose homeostatic and satiety actions of Δ-TRTX-AC1 alone, and in combination with exenatide, were then assessed in C57BL/6 mice. Synthetic Δ-TRTX-AC1 was shown to adopt a characteristic inhibitor cysteine knot (ICK)-like structure and was non-toxic to beta-cells. Δ-TRTX-AC1 evoked glucose-dependent insulin secretion from BRIN BD11 cells with bioactivity confirmed in murine islets. Insulin secretory potency was established to be dependent on KATP and Ca2+ channel beta-cell signalling. In addition, Δ-TRTX-AC1 enhanced beta-cell proliferation and provided significant protection against cytokine-induced apoptosis. When injected co-jointly with glucose in mice at a dose of 250 nmol/kg, Δ-TRTX-AC1 decreased blood-glucose levels and evoked a significant satiating effect. Moreover, whilst Δ-TRTX-AC1 did not enhance exenatide induced benefits on glucose homeostasis, the peptide significantly augmented exenatide mediated suppression of appetite. Together these data highlight the therapeutic potential of tarantula spider venom-derived peptides, such as Δ-TRTX-Ac1, for diabetes and related obesity.

PYY (3-36) protects against high fat feeding induced changes of pancreatic islet and intestinal hormone content and morphometry.

BACKGROUND: Prolonged high fat feeding negatively impacts pancreatic and intestinal morphology. In this regard, direct effects of PYY(3-36) on intestinal cell and pancreatic islet morphometry are yet to be fully explored in the setting of obesity. METHODS: We examined the influence of 21-days twice daily treatment with PYY(3-36) on these parameters in mice fed a high fat diet (HFD). RESULTS: PYY(3-36) treatment decreased food intake, body weight and circulating glucose in HFD mice. In terms of intestinal morphology, crypt depth was restored to control levels by PYY(3-36), with an additional enlargement of villi length. PYY(3-36) also reversed HFD-induced decreases of ileal PYY, and especially GLP-1, content. HFD increased numbers of PYY and GIP positive ileal cells, with PYY(3-36) fully reversing the effect on PYY cell detection. There were no obvious differences in the overall number of GLP-1 positive ileal cells in all mice, barring PYY(3-36) marginally decreasing GLP-1 villi cell immunoreactivity. Within pancreatic islets, PYY(3-36) significantly decreased alpha-cell area, whilst islet, beta-, PYY- and delta-cell areas remained unchanged. However, PYY(3-36) increased the percentage of beta-cells while also reducing percentage alpha-cell area. This was related to PYY(3-36)-induced reductions of beta-cell proliferation and apoptosis frequencies. Co-localisation of islet PYY with glucagon or somatostatin was elevated by PYY(3-36), with GLP-1/glucagon co-visualisation increased when compared to lean controls. CONCLUSION: PYY(3-36) exerts protective effects on pancreatic and intestinal morphology in HFD mice linked to elevated ileal GLP-1 content. GENERAL SIGNIFICANCE: These observations highlight mechanisms linked to the metabolic and weight reducing benefits of PYY(3-36).

Developmental Manifestations of Grief in Children and Adolescents: Caregivers as Key Grief Facilitators.

The death of a loved one represents one of the most distressing and potentially traumatic life events in childhood and adolescence. Grief reactions in youth are influenced by ongoing developmental processes and manifest differently depending on the child's age and developmental stage. These grief-related processes unfold within youths' caregiving context, as children and adolescents rely heavily on the adults in their environment to navigate and cope with the death of a loved one. Despite the field's increasing recognition of the potential for maladaptive grief reactions to impede functioning over time, few longitudinal research studies on childhood grief currently exist. In this article, we will (a) provide a brief overview of the childhood bereavement literature; (b) review the new DSM-5 and ICD-11 Prolonged Grief Disorder diagnostic criteria through a developmentally-informed lens; (c) describe how grief reactions manifest in children and adolescents of different ages through the lenses of multidimensional grief theory and relational developmental systems theory; (d) highlight key moderating factors that may influence grief in youth, and (e) discuss a primary moderating factor, the caregiving environment, and the potential mechanisms through which caregivers influence children's grief.

Preventing Mental Health Problems in Children After High Conflict Parental Separation/Divorce Study: An Optimization Randomized Controlled Trial Protocol.

Parental divorce is a childhood stressor that affects approximately 1.1 million children in the U.S. annually. The children at greatest risk for deleterious mental health consequences are those exposed to high interparental conflict (IPC) following the separation/divorce. Research shows that children's emotional security and coping efficacy mediate the impact of IPC on their mental health. Interventions targeting their adaptive coping in response to IPC events may bolster their emotional security and coping efficacy. However, existing coping interventions have not been tested with children exposed to high post-separation/divorce IPC, nor has any study assessed the effects of individual intervention components on children's coping with IPC and their mental health. This intensive longitudinal intervention study examines the mechanisms through which coping intervention components impact children's responses to interactions in interparental relationships. A 23 factorial experiment will assess whether, and to what extent, three candidate intervention components demonstrate main and interactive effects on children's coping and mental health. Children aged 9-12 (target N = 144) will be randomly assigned to one of eight combinations of three components with two levels each: (1) reappraisal (present vs. absent), (2) distraction (present vs. absent), (3) relaxation (present vs. absent). The primary outcomes are child-report emotional security and coping efficacy at one-month post-intervention. Secondary outcomes include internalizing and externalizing problems at the three-month follow-up. Based on data from this optimization phase RCT, intervention components will be selected to comprise a multi-component intervention and assessed for effectiveness in a subsequent evaluation phase RCT.

Enhancing Daily Affect in Youth Experiencing High-Conflict Parental Divorce: A Multiple Baseline Trial of an Online Prevention Program.

This study investigated the effects of a highly interactive, online cognitive-behavioral youth coping program: Children of Divorce-Coping with Divorce (CoD-CoD; Boring et al., 2015) on children exposed to high levels of interparental conflict (IPC). A multiple-baseline experimental design (N = 9) evaluated within-subject intervention effects on change in daily positive and negative affect before, during, and after the intervention (nobservations = 462). Participants were youth ages 11-16 who reported high exposure to IPC and whose parents had filed for divorce or parenting plan determinations in the prior year. A significant interaction effect indicated change in positive affect, but not negative affect, between the intervention and baseline phases. Positive affect linearly decreased during the baseline phase and flattened during the intervention phase. Results indicate that CoD-CoD was effective in interrupting a decline in youth-reported positive affect in a high-IPC sample, which may indicate a buffering effect against depression. Critical future directions include conducting large-scale randomized trials with children from high-IPC families to assess for whom the program is effective and assess long-term effects across a broad range of important outcomes.

Microbiomes of microscopic marine invertebrates do not reveal signatures of phylosymbiosis.

Animals and microorganisms often establish close ecological relationships. However, much of our knowledge about animal microbiomes comes from two deeply studied groups: vertebrates and arthropods. To understand interactions on a broader scale of diversity, we characterized the bacterial microbiomes of close to 1,000 microscopic marine invertebrates from 21 phyla, spanning most of the remaining tree of metazoans. Samples were collected from five temperate and tropical locations covering three marine habitats (sediment, water column and intertidal macroalgae) and bacterial microbiomes were characterized using 16S ribosomal RNA gene sequencing. Our data show that, despite their size, these animals harbour bacterial communities that differ from those in the surrounding environment. Distantly related but coexisting invertebrates tend to share many of the same bacteria, suggesting that guilds of microorganisms preferentially associated with animals, but not tied to any specific host lineage, are the main drivers of the ecological relationship. Host identity is a minor factor shaping these microbiomes, which do not show the same correlation with host phylogeny, or 'phylosymbiosis', observed in many large animals. Hence, the current debate on the varying strength of phylosymbiosis within selected lineages should be reframed to account for the possibility that such a pattern might be the exception rather than the rule.

Comparison of independent and combined effects of the neurotensin receptor agonist, JMV-449, and incretin mimetics on pancreatic islet function, glucose homeostasis and appetite control.

BACKGROUND: Neurotensin receptor activation augments the biosctivity of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). JMV-449, a C-terminal neurotensin-like fragment with a reduced peptide bond, represents a neurotensin receptor agonist. METHODS: The present study assessed the actions of JMV-449 on pancreatic beta-cells alone, and in combination with GIP and GLP-1. Further studies examined the impact of JMV-449 and incretin mimetics on glucose homeostasis and appetite control in mice. RESULTS: JMV-449 was resistant to plasma enzyme degradation and induced noticeable dose-dependent insulin-releasing actions in BRIN-BD11 beta-cells. In combination with either GIP or GLP-1, JMV-449 augmented (P < 0.05) the insulinotropic actions of both hormones, as well as enhancing (P < 0.001) insulin secretory activity of both incretin peptides. JMV-449 also increased beta-cell proliferation and induced significant benefits on beta-cell survival in response to cytokine-induced apoptosis. JMV-449 (25 nmol/kg) inhibited (P < 0.05-P < 0.001) food intake in overnight fasted lean mice, and enhanced (P < 0.01) the appetite supressing effects of an enzymatically stable GLP-1 mimetic. When injected co-jointly with glucose, JMV-449 evoked glucose lowering actions, but more interestingly significantly augmented (P < 0.05) the glucose lowering effects of established long-acting GIP and GLP-1 receptor mimetics. In terms of glucose-induced insulin secretion, only GIP receptor signalling was associated with increases in insulin concentrations, and this was not enhanced by JMV-449. CONCLUSION: JMV-449 is a neurotensin receptor agonist that positively augments key aspects of the biological action profile of GIP and GLP-1. GENERAL SIGNIFICANCE: These observations emphasise the, yet untapped, therapeutic potential of combined neurotensin and incretin receptor signalling for diabetes.

Weak organic acid synergy towards the prevention of catheter blockages.

BACKGROUND: Up to 50% of all long-term catheterized individuals experience recurrent episodes of urinary catheter infections and blockages, leading to urine retention, pyelonephritis and septicaemia if the catheter is left in situ. We have previously reported the synergistic activity of weak organic acid (WOA) combinations against nosocomial uropathogens. AIM: To investigate the efficacy of selected WOAs, citric acid and propionic acid, alone and in combination, on prevention of crystalline biofilm formation and catheter blockages. METHODS: Static crystallization assays and dynamic in vitro bladder model assays, with scanning electron microscopy, were performed for determination of bacterial viability, urinary pH and time to catheter blockage. FINDINGS: The rate of encrustation around the catheter eyeholes was reduced in the presence of the citric acid/propionic acid combination, extending the time to blockage three-fold. CONCLUSION: Synergistic WOA combinations identified herein represent promising alternatives to antibiotics to combat the global healthcare burden of catheter-associated urinary tract infections and related blockages.

Synergistic activity of weak organic acids against uropathogens.

BACKGROUND: Urinary tract infections (UTIs) are among the most common hospital-acquired infections, with an estimated 75% of UTIs caused by urinary catheters. In addition to the significant healthcare costs and patient morbidity, the escalating antimicrobial resistance reported among common uropathogens make the investigation of efficacious new antimicrobial strategies of urgent importance. AIM: To examine the antibacterial activity of a suite of weak organic acids (WOAs) (citric acid, malic acid, propionic acid, mandelic acid, lactic acid, benzoic acid, pyruvic acid and hippuric acid), alone and in combination, against common nosocomial uropathogens (Proteus mirabilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa). METHODS: Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm eradication concentration (MBEC), fractional inhibitory concentration index (FICI) values and kinetics of bactericidal activity of WOAs were determined by microdilution and time-kill assays. FINDINGS: All tested WOAs displayed bactericidal activities against uropathogens in their planktonic and biofilm modes of growth when used individually. Moreover, WOAs in combination displayed synergistic activity against P. mirabilis, S. aureus and E. coli, with reductions in MIC values of up to 250-fold and significant reductions in biofilm formation. CONCLUSION: The synergistic multi-mechanistic combinations identified herein are anticipated to play an important role in the treatment and prevention of catheter-associated UTIs.

Longitudinal Effects of PostDivorce Interparental Conflict on Children's Mental Health Problems Through Fear of Abandonment: Does Parenting Quality Play a Buffering Role?

In a sample of 559 children (ages 9-18), researchers investigated whether: (a) fear of abandonment mediated the association between postdivorce interparental conflict (IPC) and mental health problems, and (b) parent-child relationship quality moderated the association between IPC and fear of abandonment. Mediation analyses indicated that pretest IPC predicted fear of abandonment 3 months later, which then predicted child- and teacher-reported mental health problems 10 months later. The hypothesized protective effect of a high-quality parent-child relationship was not observed. IPC predicted fear of abandonment for all children, except for those with low- and moderate-quality father-child relationships, for whom IPC was not significantly related to fear of abandonment. Findings highlight the need to optimize child coping programs and improve parenting-after-divorce programs to reduce IPC.

The Development, Evaluation, and Implementation of Parenting-focused Prevention Programs in Collaboration with Family Court.

Promoting the well-being and best interests of children in separated and divorcing families is a shared value among family court professionals and prevention scientists who develop and evaluate intervention programs. This article chronicles the development, evaluation, and implementation of two programs - the New Beginnings Program (NBP), a parenting intervention for separated/divorcing parents and the Family Transitions Guide (FTG), an intervention designed to motivate high conflict separated/divorcing parents to attend the NBP. The development and evaluation of these programs was facilitated by a long-standing collaboration with Maricopa Family Court. We discuss the process of developing these programs, their underlying small theories, and the evaluation of their effects in randomized trials. We also describe our collaboration with the family court and ways that the court promoted the development and evaluation of these programs. Finally, we summarize lessons learned and discuss future directions to bolster the public health impact of evidence-based programs for separated/divorcing families.

Developmental cascade effects of a parenting-focused program for divorced families on competence in emerging adulthood.

This 15-year longitudinal follow-up of a randomized controlled trial of a parenting-focused preventive intervention for divorced families examined cascade models of program effects on offsprings' competence. It was hypothesized that intervention-induced improvements in parenting would lead to better academic, work, peer, and romantic competence in emerging adulthood through effects on behavior problems and competencies during adolescence. Families (N = 240) participated in the 11-session program or literature control condition when children were ages 9-12. Data were drawn from assessments at pretest, posttest, and follow-ups at 3 and 6 months and 6 and 15 years. Results showed that initial intervention effects of parenting on externalizing problems in adolescence cascaded to work outcomes in adulthood. Parenting effects also directly impacted work success. For work outcomes and peer competence, intervention effects were moderated by initial risk level; the program had greater effects on youths with higher risk at program entry. In addition, intervention effects on parenting led to fewer externalizing problems that in turn cascaded to better academic outcomes, which showed continuity into emerging adulthood. Results highlight the potential for intervention effects of the New Beginnings Program to cascade over time to affect adult competence in multiple domains, particularly for high-risk youths.

Initial Validation and Measurement Invariance of the Active Inhibition Scale Among Traumatized and Grieving Youth.

The Active Inhibition Scale (AIS; Ayers, Sandler, & Twohey, 1998) is an 11-item, self-report measure of emotional suppression among children and adolescents. Previous research with the AIS has linked emotional suppression to several clinically significant outcomes, such as posttraumatic stress symptoms (PTSS) and suicide, among trauma-exposed and bereaved youth; however, there are no published evaluations of its psychometric properties. We examined the factor structure and criterion validity of the AIS in two samples. Sample 1 included youth (M = 12.22 years, SD = 2.96, range: 6-18 years; 55.4% female) referred to an outpatient psychology clinic specializing in childhood trauma and grief. Sample 2 included youth (M = 13.18 years, SD = 2.58, range: 8-18 years; 61.8% female) referred to a community grief counseling center. Confirmatory factor analytic results supported a one-factor solution, Cronbach's α = .94. Additionally, AIS scores correlated positively with PTSS, depression, and maladaptive grief, rs = .43-.64. Evidence of factorial invariance was found across gender, race/ethnicity, and age group. Emotional suppression scores were higher among girls compared to boys, Black and Hispanic youth compared to White youth, and older compared to younger age groups. The magnitude of correlations between AIS and symptom measure scores was comparable across groups. These results support the reliability and criterion validity of the AIS with diverse youth populations and underscore the role that emotional suppression may play in explaining group differences in mental health symptoms.

A GIP/xenin hybrid in combination with exendin-4 improves metabolic status in db/db diabetic mice and promotes enduring antidiabetic benefits in high fat fed mice.

The current study has determined the ability of exendin-4 to augment the antidiabetic benefits of the recently characterised GIP/xenin hybrid, (DAla2)GIP/xenin-8-Gln. As such, combined activation of metabolic pathways linked to various gut derived hormones has been shown to exert complementary beneficial metabolic effects in diabetes. (DAla2)GIP/xenin-8-Gln and exendin-4 were administered twice daily to high fat fed (HFF) or db/db mice for 28 days and antidiabetic benefits assessed. Persistence of beneficial metabolic effects in HFF mice was also examined. Twice-daily injection of (DAla2)GIP/xenin-8-Gln for 28 days in HFF mice significantly reduced energy intake, body weight, circulating glucose, HbA1c and improved glucose tolerance and insulin sensitivity. Overall pancreatic islet, alpha- and beta-cell areas were reduced, with concurrent reduction in alpha- and beta-cell proliferation that was more apparent in the combined treatment group. Addition of exendin-4 to (DAla2)GIP/xenin-8-Gln therapy did not significantly improve metabolic control. Remarkably, beneficial effects were still evident 14 days following complete cessation of peptide administration. Thus, circulating glucose and insulin, HbA1c concentrations and glucose tolerance were still significantly improved when compared to control HFF mice on day 42, with minimal changes to pancreatic islet architecture. In contrast to HFF mice, combined treatment of db/db mice with (DAla2)GIP/xenin-8-Gln plus exendin-4 was required to induce beneficial effects on key metabolic parameters, which were not observed with either treatment alone. This included improvements in glucose tolerance and insulin sensitivity, but no effect on pancreatic architecture. These studies highlight the clear, and persistent, metabolic advantages of sustained activation of GLP-1 receptors, alongside concurrent activation of related GIP and xenin cell signalling pathways, in diabetes.

Saturated Raman scattering for sub-diffraction-limited imaging.

We present a scheme for a sub-diffraction-limited Raman microscope. The scheme combines the concept from stimulated depletion microscopy with femtosecond stimulated Raman scattering. The suppression of the Raman signal in a three-beam setup with only two involved wavelength-components was accomplished by the saturation of the Raman scattering. A reduction of the Raman signal of up to 79% could be measured with only a single Raman resonance involved. Based on this signal suppression, a resolution enhancement by a factor of 2 could be verified in a first proof-of-concept measurement, opening up a pathway toward label-free sub-diffraction-limited imaging.

Antidiabetic effects and sustained metabolic benefits of sub-chronic co-administration of exendin-4/gastrin and xenin-8-Gln in high fat fed mice.

The present study has examined the antidiabetic effects of 21 days co-administration of xenin-8-Gln with the dual-acting fusion peptide, exendin-4/gastrin, as well as persistence of beneficial metabolic benefits, in high fat fed (HFF) mice. Xenin-8-Gln, exendin-4 and gastrin represent compounds that activate receptors of the gut-derived hormones, xenin, glucagon-like peptide-1 (GLP-1) and gastrin, respectively. Twice-daily administration of exendin-4/gastrin, xenin-8-Gln or a combination of both peptides significantly reduced circulating glucose, HbA1c and cumulative energy intake. Combination therapy with xenin-8-Gln and exendin-4/gastrin increased circulating insulin. All HFF mice treated with exendin-4/gastrin presented with body weight similar to lean control mice on day 21. Each treatment improved glucose tolerance and the glucose-lowering actions of glucose dependent insulinotropic polypeptide (GIP), as well as augmenting glucose- and GIP-induced insulin secretion, with benefits being most prominent in the combination group. Administration of exendin-4/gastrin alone, and in combination with xenin-8-Gln, increased pancreatic insulin content and improved the insulin sensitivity index. Pancreatic beta-cell area was significantly increased, and alpha cell area decreased, by all treatments, with the combination group also displaying enhanced overall islet area. Notably, metabolic benefits were generally retained in all groups of HFF mice, and especially in the combination group, following discontinuation of the treatment regimens for 21 days. This was associated with maintenance of increased islet and beta-cell areas. Together, these data confirm the antidiabetic effects of co-activation of GLP-1, gastrin and xenin cell signalling pathways, and highlight the sustainable benefits this type of treatment paradigm can offer in T2DM.