Quantifiable Changes in the Submental Area and Mandible Border After Dual-Modality Treatment With ATX-101 and VYC-20L for Overall Improvement in Jawline Contour.

BACKGROUND: A phase 4, prospective, open-label, multicenter study showed that treatment with deoxycholic acid injections (ATX-10) followed by a hyaluronic acid filler (VYC-20L) is safe and effective for reducing submental fullness and improving jawline definition. OBJECTIVE: To quantify changes in the jawline and submental area using 3-dimensional (3D) photogrammetry and conduct an immunohistochemical analysis of submental tissue.  Methods: Participants received 1 to 6 ATX-101 treatments (8 weeks apart) followed by VYC-20L (optional touch-up after 14 days). Changes from baseline in jawline and submental volumes, submental major and minor strain events, submental skin displacement, and submental angles were quantified using photogrammetry. Submental skin biopsies (N=13) were excised for histologic analysis. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: Fifty-three participants were treated. From baseline to the final study visit, the mean volume increased for the jawline and decreased for the submental area. There was a larger percentage change from baseline in the minor versus major strain event, indicating greater skin surface compression than expansion within the submental area. Mean change from baseline in submental skin position indicated superior and posterior movement from a lateral perspective, while the mean submental angle decreased between baseline and exit. Collagen I and III expression significantly increased from baseline (P<0.05). All participants reported at least 1 TEAE; the majority were mild or moderate in severity. CONCLUSIONS: Dual-modality treatment with ATX-101 and VYC-20L reduces submental fat and improves jawline definition with quantifiable changes in jawline volume, submental volume, strain, skin displacement, and angle, as well as collagen expression. J Drugs Dermatol. 2024;23(1):1325-1331.        doi:10.36849/JDD.7458.

Narrative review of inpatient nutritional management of anorexia nervosa with management recommendations for Australian tertiary health services.

BACKGROUND: Patients with anorexia nervosa (AN) may experience life-threatening malnutrition-related complications requiring inpatient medical stabilisation. Several management guidelines have been developed but discrepancies exist because of limited high-level evidence. AIMS: To review the evidence base for recommendations contained in Victorian health services guidelines for the nutritional management of inpatients with AN. METHODS: MEDLINE and Embase databases were searched for published studies on the nutritional management of inpatients with AN, combined with a manual search through citations. Studies including patients with AN aged 16 years and older were included. Case reports, small case series of <10 patients, studies of nonmedical management and studies with an exclusive paediatric population were excluded. The search results were compared with AN inpatient medical management guidelines sourced from large tertiary health services across Victoria, Australia. RESULTS: The search yielded 584 studies, subsequently reduced to nine studies using the inclusion and exclusion criteria. The results suggest that commencing refeeding at a higher caloric value allows faster weight gain and shorter hospitalisation. Enteral tube feeding is preferential to parenteral nutrition because of infrequent and milder complications. Zinc supplementation showed a doubled rate of body mass index increase compared with placebo. Comparison with Victorian health services guidelines revealed inconsistent recommendations for high-calorie refeeding and micronutrient supplementation. CONCLUSION: The evidence supports high-calorie refeeding of 2000 kcal/day in AN inpatient medical management and zinc supplementation in improving the rate of weight restoration. This is inconsistently reflected in different Victorian health services guidelines. Updated national consensus guidelines could assist in improving consistency of evidence-based health care.

Transition from a renal paediatric clinic to an adult clinic: Perspectives of adolescents and young adults, parents and health professionals.

The management of chronic kidney disease is complex. With disease management being the responsibility of parents in the paediatric renal clinic, the responsibility is gradually shifted to adolescents and young adults during the transition to adult care. This multi-perspective qualitative study aimed to explore the experiences of adolescents and young adults, their parents and health professionals to gain an insight into transitional care. Focussing on the transition process and transfer to adult care, 18 adolescents and young adults and eight mothers participated in individual semi-structured interviews. Additionally, three focus groups were conducted with 20 multidisciplinary health professionals. Data were transcribed verbatim and analysed thematically. Similar responses from adolescents and young adults and mothers included the reluctance to leave the paediatric health service. Mothers found the transition to adult care more challenging than the adolescents and young adults. While health professionals acknowledged that engaging adolescents and young adults in their own care was challenging, they believed parents had an important role in facilitating their child's independence. This study highlights that health professionals in both paediatric and adult health services need to work collaboratively. However, importantly, health professionals need to be mindful that parents require an equal amount of engagement as adolescents and young adults, if not more, to mitigate parental barriers in achieving a successful transfer.

Dialysis and driving: an anonymous survey of patients receiving dialysis for end-stage kidney disease.

BACKGROUND: Driving is a complex task requiring multiple cognitive domains and the musculoskeletal system. Cognitive dysfunction is associated with driving impairment. Dialysis patients are known to have a high prevalence of cognitive impairment and other comorbidities, and may be at risk of driving impairment. No Australian guidelines address driving safety in dialysis patients. AIMS: To estimate the proportion of dialysis patients who were driving and those at risk of driving impairment, and to investigate the agreement between objective and subjective markers of risk. METHODS: This single-centre study involved dialysis patients voluntarily completing two questionnaires relating to risk of driving impairment; the first questionnaire focussed on objective markers, and the second questionnaire focussed on subjective markers. Risk of driving impairment was established using pre-determined criteria, and the agreement between objective and subjective markers was estimated using Cohen kappa. RESULTS: A total of 44.8% (99/221) of patients participated; 76.8% (76/99) of participants were driving, and 76.3% (58/76) of drivers were at risk of driving impairment. Factors associated with at-risk driving included post dialysis dizziness, leg weakness or numbness, falling asleep while driving and hypoglycaemia. Sixteen patients reported collisions since commencing dialysis. The questionnaires displayed slight agreement (Cohen kappa = 0.20) between objective and subjective markers. CONCLUSIONS: Dialysis patients are at risk of driving impairment based on self-reported questionnaire responses. Discrepancies between patients' perceptions and objective markers were apparent. Further research into appropriate risk assessments, as well as development of guidelines to aid in determining driving safety in dialysis patients, is needed.

Pre-eclampsia is associated with altered expression of the renal sodium transporters NKCC2, NCC and ENaC in urinary extracellular vesicles.

Pre-eclampsia is a hypertensive disorder of pregnancy characterised by hypertension and sodium retention by the kidneys. To identify changes in sodium uptake proteins in the tubules of the distal nephron, we studied their expression in urinary extracellular vesicles or exosomes (uEVs). Urine was collected from women with pre-eclampsia or during normal pregnancy, and from healthy non-pregnant controls. uEVs were isolated by centrifugation and analyzed by Western blot. Expression, proteolytic cleavage and phosphorylation was determined by densitometric analysis normalized to the exosome marker CD9. Results showed a significant increase in phosphorylation of the activating S130 site in NKCC2, the drug target for frusemide, in women with pre-eclampsia compared with normal pregnant women. Phosphorylation of the activating sites T101/105 in NKCC2 was similar but the activating T60 site in NCC, the drug target for thiazide diuretics, showed significantly less phosphorylation in pre-eclampsia compared with normal pregnancy. Expression of the larger forms of the α subunit of ENaC, the drug target for amiloride, was significantly greater in pre-eclampsia, with more fragmentation of theγ subunit. The differences observed are predicted to increase the activity of NKCC2 and ENaC while reducing that of NCC. This will increase sodium reabsorption, and so contribute to hypertension in pre-eclampsia.

Lifetime risk of end-stage kidney disease in living donors for paediatric kidney transplant recipients in Australia and New Zealand - a retrospective study.

Living kidney donors (LKD) for paediatric kidney transplant recipients (KTR) have a heightened motivation to donate for emotional reasons and the clear health benefits to the KTR. We hypothesized that the cohort of LKD for paediatric KTR (LKD-P) includes motivated young parents with a higher lifetime end-stage kidney disease (ESKD) risk compared to adult KTR (LKD-A). Data from the Australia and New Zealand Dialysis and Transplant LKD Registry (2004-2015) was analysed to compare baseline characteristics and predonation ESKD risk in LKD-P (n = 315) versus LKD-A (n = 3448). LKD-P were younger (median age 42 vs. 50 years; P < 0.001) and had a marginally higher lifetime ESKD risk (median 0.44% vs. 0.40%; P < 0.01), with a similar proportion of LKD exceeding 1% risk threshold (5.4% vs. 5.6%; P = NS). Compared to grandparents as LKD-P, parents (median age 41 vs. 59 years; P < 0.001) had a higher lifetime ESKD (0.44% vs. 0.25%; P < 0.001). Although unique benefits to paediatric KTR justify the minor increase in lifetime ESKD risk in young parents, carefully selected grandparents are an alternative LKD-P option, allowing parents to donate for subsequent transplants.

Use of a new end-stage kidney disease risk calculator in the Kidney Disease Improving Global Outcomes guideline to evaluate the impact of different living kidney donor candidate assessments.

AIM: The Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends the incorporation of a new risk calculator that quantifies the end-stage kidney disease (ESKD) risk based on a composite profile of risk factors in living kidney donor candidates (LKDC). We compared the ESKD risk estimates in previously declined versus accepted LKDC to evaluate the predictive capacity and potential impact of this tool. METHODS: Baseline 15 year and lifetime ESKD risk estimates without donation were calculated using the risk calculator for LKDC assessed from two centres between 2007 and 2015. LKDC suitability based on the proposed KDIGO and the existing Caring for Australasians with Renal Impairment national guidelines was compared. RESULTS: Median 15 year ESKD risk was 0.14% (IQR 0.09-0.31%) in declined LKDC (n=59) versus 0.10% (0.07-0.14%) in accepted LKDC (n=89) (P<0.001). Lifetime risk was similar: 0.39% (0.23-0.80%) versus 0.35% (0.22-0.56%), respectively; however, declined LKDC had a higher 98% risk percentile value (8.19% vs 1.02%) and were more likely to exceed a 1% ESKD risk threshold (15% vs 1%; P<0.01). The calculator captured reasons for declining donation in only 39% of LKDC; 46.9% of LKDC with Caring for Australasians with Renal Impairment contraindications were reclassified as having an acceptable (≤1%) lifetime risk and no KDIGO contraindications, primarily related to a lower pre-donation glomerular filtration rate or controlled hypertension with obesity. CONCLUSION: Declined LKDC had a higher 15 year but similar lifetime ESKD risk. However, the calculator successfully differentiated declined LKDC with a lifetime risk >1%. This risk calculator appears to complement but not replace clinical evaluation.

Obesity-Related Chronic Kidney Disease-The Role of Lipid Metabolism.

Obesity is an independent risk factor for chronic kidney disease (CKD). The mechanisms linking obesity and CKD include systemic changes such as high blood pressure and hyperglycemia, and intrarenal effects relating to lipid accumulation. Normal lipid metabolism is integral to renal physiology and disturbances of renal lipid and energy metabolism are increasingly being linked with kidney disease. AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) are important regulators of fatty acid oxidation, which is frequently abnormal in the kidney with CKD. A high fat diet reduces renal AMPK activity, thereby contributing to reduced fatty acid oxidation and energy imbalance, and treatments to activate AMPK are beneficial in animal models of obesity-related CKD. Studies have found that the specific cell types affected by excessive lipid accumulation are proximal tubular cells, podocytes, and mesangial cells. Targeting disturbances of renal energy metabolism is a promising approach to addressing the current epidemic of obesity-related kidney disease.

AMPK couples plasma renin to cellular metabolism by phosphorylation of ACC1.

Salt reabsorption is the major energy-requiring process in the kidney, and AMP-activated protein kinase (AMPK) is an important regulator of cellular metabolism. Mice with targeted deletion of the ß1-subunit of AMPK (AMPK-ß1(-/-) mice) had significantly increased urinary Na(+) excretion on a normal salt diet. This was associated with reduced expression of the ß-subunit of the epithelial Na(+) channel (ENaC) and increased subapical tubular expression of kidney-specific Na(+)-K(+)-2Cl(-) cotransporter 2 (NKCC2) in the medullary thick ascending limb of Henle. AMPK-ß1(-/-) mice fed a salt-deficient diet were able to conserve Na(+), but renin secretion increased 180% compared with control mice. Cyclooxygenase-2 mRNA also increased in the kidney cortex, indicating greater signaling through the macula densa tubular salt-sensing pathway. To determine whether the increase in renin secretion was due to a change in regulation of fatty acid metabolism by AMPK, mice with a mutation of the inhibitory AMPK phosphosite in acetyl-CoA carboxylase 1 [ACC1-knockin (KI)(S79A) mice] were examined. ACC1-KI(S79A) mice on a normal salt diet had no increase in salt loss or renin secretion, and expression of NKCC2, Na(+)-Cl(-) cotransporter, and ENaC-ß were similar to those in control mice. When mice were placed on a salt-deficient diet, however, renin secretion and cortical expression of cyclooxygenase-2 mRNA increased significantly in ACC1-KI(S79A) mice compared with control mice. In summary, our data suggest that renin synthesis and secretion are regulated by AMPK and coupled to metabolism by phosphorylation of ACC1.

Exposure to Interpersonal Violence and Its Associations With Psychiatric Morbidity in a U.S. National Sample: A Gender Comparison.

OBJECTIVES: We examine gender differences in population rates of various types of interpersonal violence in a U.S. national sample and investigate gender as a moderator of the associations between interpersonal violence and lifetime mental disorders and suicide attempts. METHODS: Data were drawn from the National Comorbidity Survey-Replication study; 5,692 women and men completed interviews assessing lifetime exposure to nine types of interpersonal violence, Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) mental health diagnoses, and suicide attempts. RESULTS: Approximately 46% of women and 42% of men reported one or more types of interpersonal violence. Women were more likely to experience kidnapping, physical assault by an intimate partner, rape, sexual assault, and stalking, whereas men were more likely to experience mugging or physical assault by someone other than parents or an intimate partner. Interpersonal violence was associated with risk for many mental disorders and attempted suicide. Although women were at higher risk for several forms of interpersonal violence, the impact of interpersonal violence on mental health outcomes did not vary by gender. CONCLUSIONS: It is clearly important to identify and provide mental health treatment to women after interpersonal violence exposure. Findings also underscore the need for prevention and intervention efforts for women and men, including routine screening for interpersonal violence by health care providers and appropriate treatment to address mental health conditions.

A novel process for integrating patient stories into patient education interventions: incorporating lessons from theater arts.

OBJECTIVE: Patient narratives, or stories, are an effective means of educating patients because they increase personal relevance and may reduce counter-arguing. However, such stories must seamlessly combine evidenced-based health information while being true to real patient experiences. The purpose of this paper is to describe the process of developing an educational intervention using African-American patients' success stories controlling hypertension. METHODS: We identified a process to address stories development challenges. RESULTS: (1) To help identify story tellers, we conducted a literature review and subsequently streamlined the process of storyteller identification through screening and telephone interviews. (2) To better elicit stories, we consulted with experts in storytelling and incorporated principles from theater. (3) To select stories, we used intervention mapping to map the intervention to theory and key clinical concepts, and also engaged members of the target community to ensure scientific criteria and maintain authenticity. CONCLUSION: Using personal narratives as intervention requires weaving together science, theory and clinically sound content, while still being true to the art of storytelling. Through a careful process of identifying storytellers and story selection and drawing upon theater arts, creating stories for intervention can be streamlined while meeting the goals of authenticity and scientific soundness.

The sustainability of new programs and innovations: a review of the empirical literature and recommendations for future research.

BACKGROUND: The introduction of evidence-based programs and practices into healthcare settings has been the subject of an increasing amount of research in recent years. While a number of studies have examined initial implementation efforts, less research has been conducted to determine what happens beyond that point. There is increasing recognition that the extent to which new programs are sustained is influenced by many different factors and that more needs to be known about just what these factors are and how they interact. To understand the current state of the research literature on sustainability, our team took stock of what is currently known in this area and identified areas in which further research would be particularly helpful. This paper reviews the methods that have been used, the types of outcomes that have been measured and reported, findings from studies that reported long-term implementation outcomes, and factors that have been identified as potential influences on the sustained use of new practices, programs, or interventions. We conclude with recommendations and considerations for future research. METHODS: Two coders identified 125 studies on sustainability that met eligibility criteria. An initial coding scheme was developed based on constructs identified in previous literature on implementation. Additional codes were generated deductively. Related constructs among factors were identified by consensus and collapsed under the general categories. Studies that described the extent to which programs or innovations were sustained were also categorized and summarized. RESULTS: Although "sustainability" was the term most commonly used in the literature to refer to what happened after initial implementation, not all the studies that were reviewed actually presented working definitions of the term. Most study designs were retrospective and naturalistic. Approximately half of the studies relied on self-reports to assess sustainability or elements that influence sustainability. Approximately half employed quantitative methodologies, and the remainder employed qualitative or mixed methodologies. Few studies that investigated sustainability outcomes employed rigorous methods of evaluation (e.g., objective evaluation, judgement of implementation quality or fidelity). Among those that did, a small number reported full sustainment or high fidelity. Very little research has examined the extent, nature, or impact of adaptations to the interventions or programs once implemented. Influences on sustainability included organizational context, capacity, processes, and factors related to the new program or practice themselves. CONCLUSIONS: Clearer definitions and research that is guided by the conceptual literature on sustainability are critical to the development of the research in the area. Further efforts to characterize the phenomenon and the factors that influence it will enhance the quality of future research. Careful consideration must also be given to interactions among influences at multiple levels, as well as issues such as fidelity, modification, and changes in implementation over time. While prospective and experimental designs are needed, there is also an important role for qualitative research in efforts to understand the phenomenon, refine hypotheses, and develop strategies to promote sustainment.

Low salt concentrations activate AMP-activated protein kinase in mouse macula densa cells.

The energy-sensing kinase AMP-activated protein kinase (AMPK) is associated with the sodium-potassium-chloride cotransporter NKCC2 in the kidney and phosphorylates it on a regulatory site in vitro. To identify a potential role for AMPK in salt sensing at the macula densa, we have used the murine macula densa cell line MMDD1. In this cell line, AMPK was rapidly activated by isosmolar low-salt conditions. In contrast to the known salt-sensing pathway in the macula densa, AMPK activation occurred in the presence of either low sodium or low chloride and was unaffected by inhibition of NKCC2 with bumetanide. Assays using recombinant AMPK demonstrated activation of an upstream kinase by isosmolar low salt. The specific calcium/calmodulin-dependent kinase kinase inhibitor STO-609 failed to suppress AMPK activation, suggesting that it was not part of the signal pathway. AMPK activation was associated with increased phosphorylation of the specific substrate acetyl-CoA carboxylase (ACC) at Ser(79), as well as increased NKCC2 phosphorylation at Ser(126). AMPK activation due to low salt concentrations was inhibited by an adenovirus construct encoding a kinase dead mutant of AMPK, leading to reduced ACC Ser(79) and NKCC2 Ser(126) phosphorylation. This work demonstrates that AMPK activation in macula densa-like cells occurs via isosmolar changes in sodium or chloride concentration, leading to phosphorylation of ACC and NKCC2. Phosphorylation of these substrates in vivo is predicted to increase intracellular chloride and so reduce the effect of salt restriction on tubuloglomerular feedback and renin secretion.

Regulation of the renal-specific Na+-K+-2Cl- co-transporter NKCC2 by AMP-activated protein kinase (AMPK).

The renal-specific NKCC2 (Na+-K+-2Cl- co-transporter 2) is regulated by changes in phosphorylation state, however, the phosphorylation sites and kinases responsible have not been fully elucidated. In the present study, we demonstrate that the metabolic sensing kinase AMPK (AMP-activated protein kinase) phosphorylates NKCC2 on Ser126 in vitro. Co-precipitation experiments indicated that there is a physical association between AMPK and the N-terminal cytoplasmic domain of NKCC2. Activation of AMPK in the MMDD1 (mouse macula densa-derived 1) cell line resulted in an increase in Ser126 phosphorylation in situ, suggesting that AMPK may phosphorylate NKCC2 in vivo. The functional significance of Ser126 phosphorylation was examined by mutating the serine residue to an alanine residue resulting in a marked reduction in co-transporter activity when exogenously expressed in Xenopus laevis oocytes under isotonic conditions. Under hypertonic conditions no significant change of activity was observed. Therefore the present study identifies a novel phosphorylation site that maintains NKCC2-mediated transport under isotonic or basal conditions. Moreover, the metabolic-sensing kinase, AMPK, is able to phosphorylate this site, potentially linking the cellular energy state with changes in co-transporter activity.

Photosensitive dermatitis due to sunscreen allergy in a child.

We report a case of photoallergic contact dermatitis to two sunscreen agents, methoxycinnamate and oxybenzone, occurring in a 6-year-old Asian boy.