Additional Treatment Research Articles

Sleep disturbance and menopause.

Sleep problems are among the most prevalent and bothersome symptoms of menopause. This review characterizes menopausal sleep disturbances, describes biopsychosocial predictors, and summarizes the evidence supporting pharmacological and nonpharmacological treatment options. Recent studies found that sleep changes are early indicators of perimenopause and sought to disentangle the respective impacts of menopausal status, hot flashes (HFs), and changes in reproductive hormones on peri-/postmenopausal sleep problems. Both HFs and reproductive hormones predicted sleep problems, but neither solely accounted for the myriad changes in sleep, thus highlighting the contribution of additional biopsychosocial risk factors. Inconsistencies across studies were likely due to differences in study design and methodology, participants' menopausal stage, and the presence of sleep complaints. Recent studies support the use of psychological (cognitive-behavioral therapy for insomnia) and pharmacological (e.g., neurokinin B antagonists) treatments in addition to hormone therapy. Sleep problems are common and of critical import to women during the menopausal transition, significantly influencing treatment preferences and satisfaction. Thus, sleep problems should be routinely assessed from a biopsychosocial perspective and treated with evidence-based interventions throughout menopause. Treatment selection should be based on diagnosis and careful assessment.

Understanding the impact of host plant factors on the oviposition behaviour of the cabbage stem flea beetle (Psylliodes chrysocephala)

AbstractFor many phytophagous insects, oviposition plays a key role in the selection of an appropriate host. A more comprehensive understanding of the factors influencing this behaviour in pest insects provides a basis for the development of new management strategies. Herein, the determinants of oviposition were assessed in the cabbage stem flea beetle, Psylliodes chrysocephala (Coleoptera: Chrysomelidae), an insect specialized on the Brassicaceae family and a major pest of oilseed rape crops in Europe. To this end, a controlled condition experiment was conducted, in which a range of host plants exhibiting varying degrees of acceptability for feeding were presented to mature females. A superior host, Brassica rapa pekinensis, an intermediate one, Brassica napus, and a non‐host plant, Iberis amara, were used. An additional treatment involved wrapping the plants in micro‐perforated plastic bags to prevent feeding on aerial parts. The results demonstrated that contact with the host plant, and more particularly feeding, stimulated oviposition, with this effect being more pronounced in B. napus. Indeed, for the same amount of feeding, females laid significantly more eggs when feeding on B. napus than when feeding on B. rapa pekinensis. Additionally, a sequential experiment demonstrated that the intensity of oviposition is subject to rapid adaptive changes, as it is exclusively dependent on the current dietary conditions, with no influence of past dietary regimens. The quantification of macronutrients indicated the potential influence of plant‐digestible carbohydrates on these outcomes. Further investigation is required to determine the impact of the plant nutritional quality and defences on oviposition.

Snowfall Change Had Different Effects on Litter Decomposition for Two Typical Desert Species in Different Periods

In desert ecosystems, litter decomposition is the primary source of soil nutrients and is strongly affected by extreme climate events, which may influence desert plant survival and species diversity. To date, the effects of snowfall changes on litter decomposition in desert species remain poorly understood. Here, a snowfall manipulation experiment was conducted in Northwest China that included snowfall addition and removal treatments, as well as a natural snowfall control. Compared to the control, snowfall addition increased the amount of litter mass lost for Salsola passerina and Reaumuria soongarica during the snow-covered period by 21.54% and 21.8%, respectively. In contrast, snowfall addition effects differed between species during the snow-free period. More carbon was released from the S. passerina litter in the snowfall addition treatment during the snow-free period. Similarly, during the snow-covered period, more carbon and nitrogen were released from the R. soongorica litter in the snowfall addition treatment. Overall, the proportion of litter mass lost (from the annual total) increased with snowfall addition in the snow-covered period but was reduced with snowfall addition in the snow-free period. In the snow-covered period, the snowfall addition treatment affected litter mass loss to the same extent in both species but impacted S. passerina more strongly than R. soongorica in the snow-free period due to differences in soil urease activity. Changes in snowfall, therefore, significantly influenced litter decomposition in both desert species, but these effects differed between the snow-covered and snow-free period, particularly for litter with a higher C:N ratio.

Resection of Meningiomas Invading the Cavernous Sinus: Treatment Strategy and Clinical Outcomes

Background/Objectives: Resection of tumors invading the cavernous sinus (CS) carries a risk of injury to the cranial nerves and internal carotid artery. Therefore, radical surgery involving lesions around the CS remains challenging, especially for lesions invading the CS, optic sheath, and oculomotor cave. Here, we describe a surgical strategy for meningiomas invading these structures and report on the clinical outcomes. Methods: Surgical resection was indicated in patients with neurological symptoms or rapid tumor growth for the restoration of cranial nerve function. We investigated 13 patients who had preoperative images of CS invasion, underwent surgical resection, and were followed-up with magnetic resonance imaging for at least 1 year between July 2017 and July 2024. Their preoperative symptoms, postoperative course, adjuvant therapy, postoperative complications, degree of resection, and recurrence were evaluated. Results: The mean patient age was 59.1 years (range, 23–73 years), and 10 were female. Major preoperative symptoms included oculomotor nerve paresis in 8 patients (61.5%), abducens nerve paresis in 6 (46.2%), visual disturbance in 7 (53.8%), and brain swelling in 3 (23.1%). These symptoms improved at least partially after surgery in 7 (87.5%), 5 (83.3%), 7 (100%), and 3 (100%) patients, respectively. Major postoperative complications included contralateral visual deterioration in 1 patient (7.7%) and brief transient slight hemiparesis caused by internal carotid vasospasm or dissection in 2 (15.4%). Four patients with residual atypical meningioma in the CS underwent intensity-modulated radiotherapy (IMRT). The lesions in 6 patients recurred or regrew, resulting in additional treatment with stereotactic radiosurgery in 2 patients, IMRT in 3, and resection in 1. Conclusions: Our surgical strategy for the surgical resection of meningiomas in and around the CS for the restoration of cranial nerve function is safe and effective, with only transient acceptable injuries. Even if the tumor in the CS is too stiff to be removed, it is important to open the optic nerve sheath and oculomotor cave widely to effectively remove the tumor.

A Long-Term Retrospective Observational Clinical Study Evaluating the Efficacy of Plasma Rich in Growth Factors (PRGF) in the Treatment of Back Pain.

Chronic back pain is a long-lasting disorder that is significantly associated with a reduction in the quality of life. Previously, the efficacy of intradiscal and epidural injections of plasma rich in growth factors (PRGF) was demonstrated at 6months. The objective of this study was to retrospectively examine the medical records of these patients in order to determine whether the observed improvement at the 6-month follow-up was sustained over time. PRGF efficacy was evaluated using validated questionnaires: Core Outcome Measure Index (COMI) Pain score, COMI Disability score, COMI total score, and Oswestry Disability Index (ODI). Furthermore, an evaluation was conducted to determine whether the patients had undergone additional treatments. the results demonstrated that 85.2% of the 27 patients who were enrolled exhibited sustained improvement across all scales over a median follow-up period of 24months. The results of all questionnaires administered at 24months exhibited statistically significant differences when compared to the baseline data (p < 0.01). Furthermore, there were no statistically significant differences between the results reported at 6months and those at 24months (p > 0.05). the results of this retrospective study demonstrate that treatment of chronic back pain with PRGF was effective in maintaining pain reduction and improving function for at least 24 months after the end of treatment.

A straightforward process manipulates the dramatic morphological changes of DNA rolling circle amplification products.

Rolling circle amplification (RCA) is a widely used method for the synthesis of DNA nanoparticles and macro-hydrogels. Several strategies, including oscillation-promoted entanglement of DNA chains, multi-round chain amplification, hybridization between DNA chains, and hybridization with functional moieties, were applied to synthesize DNA macro-hydrogels; alternatively, flower-like nanoparticles were also produced. Here we report a straightforward yet effective method to manipulate the morphology of RCA products from nanoparticles to 3D hydrogels using an additional cold treatment step of the circular DNA template prior to elongation using phi29 DNA polymerase. This process induces a minor aggregation of the circular DNA template, significantly enhancing the entanglement of DNA chains in subsequent steps. Compared to contemporary synthesis methods for RCA-based macro-hydrogels, our technique provides milder reaction conditions, shorter reaction time, and a more straightforward system. Notably, our method eliminates the need for oscillation during amplification and requires only a single round of RCA with a single type of circular DNA, thereby simplifying the synthesis process.

Influence of Heat Treatment on Properties and Microstructure of EN AW-6082 Aluminium Alloy Drawpieces After Single-Point Incremental Sheet Forming

An EN AW-6082 aluminium alloy is one of the 6000 series aluminium alloys with the highest strength properties. Due to its favourable strength-to-density ratio, it is used, among others, in the automotive and aviation applications. It is also characterised by good formability, especially in the annealed condition. This article presents the results of investigations on the possibility of forming a 2 mm thick EN AW-6082 alloy sheet using the incremental sheet-forming process depending on the material condition (O, W, T4, T6). The microstructure of the material after heat treatment and the mechanical properties of the workpiece material in as-received state, as well as after forming, were examined. Additionally, for selected cases, additional heat treatment of the drawpieces was performed to improve their mechanical strength. The values of the limit-forming angle were determined for the materials tested. The values of this angle varied from 69° for the annealed sheet to 61° for the material in the T6 condition. The highest yield stress (YS) and ultimate tensile strength (UTS) were found for sheets (YS = 305 MPs and UTS = 324 MPa) and the artificially aged drawpieces (YS = 333 MPa and UTS = 390 MPa). Additional ageing after incremental sheet forming resulted in an increase in strength properties compared to drawpieces without additional heat treatment only in the case of drawpieces made of sheet metal after the solutionising and in T4 condition.

Highlights on gastroesophageal tumors: the comeback of FLOT

Summary This article aims to summarize the highlights of the two largest global congresses of 2024 with respect to gastroesophageal tumors. The triplet chemotherapy combination known as FLOT (5-fluorouracil, leucovorin, oxaliplatin, docetaxel), used as perioperative chemotherapy, was demonstrated to improve overall and disease-free survival in resectable gastroesophageal cancer patients some time ago. Despite being standard for this patient population, many questions for different scenarios remain open: Is FLOT also efficacious in patients with esophageal or gastroesophageal junction adenocarcinoma when compared to neoadjuvant chemoradiotherapy? Is FLOT a feasible chemotherapy option for oligometastatic patients, thereby contributing to the overall survival as “neoadjuvant” treatment before palliative resection? Can the efficacy of FLOT be strengthened by applying additional radiation treatment to patients with gastroesophageal adenocarcinoma? Is FLOT really necessary in the adjuvant setting for all patients, or can the adjuvant treatment be guided based on pathological response rates? These questions were answered to some extent in the ESOPEC and RENAISSANCE trials at the American Society of Clinical Oncology (ASCO) meeting and the TOPGEAR and SPACE-FLOT trials at European Society for Medical Oncology (ESMO) meeting. Many other FLOT-related studies for resectable as well as metastatic gastroesophageal cancer patients are yet to come.

Thiazides as an additional antiproteinuric treatment in young patients with Alport syndrome

Thiazides as an additional antiproteinuric treatment in young patients with Alport syndrome

Effectiveness of Paracetamol in Treating Hemodynamically Significant Patent Ductus Arteriosus in Preterm Newborns

Background: Patent ductus arteriosus (PDA) is a common condition in preterm infants, often requiring medical intervention for closure. Traditional treatments such as indomethacin and ibuprofen are associated with adverse effects, prompting the exploration of alternative therapies. Paracetamol (acetaminophen) has emerged as a potential alternative with a favorable safety profile, but its efficacy in preterm infants remains under investigation. Aim: The aim of this study is to evaluate the efficacy of paracetamol in the management of hemodynamically significant PDA in preterm newborns, focusing on ductal closure rates, respiratory improvement, and the need for further interventions. Methods: This prospective observational study was conducted at Jawaharlal Nehru Medical College &amp; Hospital, enrolling 50 preterm infants diagnosed with hemodynamically significant PDA. Paracetamol (15 mg/kg iv every 6 hours) was administered for 120 hours. Clinical outcomes, including PDA closure, respiratory status, and the need for additional treatments, were monitored. Data were analyzed using SPSS version 23.0. Results: Out of 50 infants, 35 (70%) achieved complete PDA closure after 120 hours of paracetamol therapy. Respiratory improvement was observed in 28 (56%) infants, with a reduction in oxygen requirements. The mean duration of paracetamol treatment was 4.8 ± 0.9 days, and the mean NICU stay was 14.3 ± 3.2 days. No severe adverse events were noted, though 3 (6%) infants experienced mild transient liver enzyme elevation. Conclusion: Paracetamol was found to be an effective treatment for PDA in preterm infants, with high closure rates and a favorable safety profile compared to traditional treatments. It may serve as a viable alternative to indomethacin or surgical ligation in managing PDA. Recommendations: Paracetamol should be considered as a first-line pharmacological treatment for PDA in preterm infants, particularly in cases where traditional treatments are contraindicated or carry a high risk of adverse effects. Further studies with larger cohorts are needed to confirm these findings and assess long-term outcomes. Keywords: Paracetamol, Patent Ductus Arteriosus, Preterm Infants, Pharmacological Treatment, Neonatal Care.

Optimizing Pyroxasulfone-Coated Fertilizer in Cotton

Abstract Two studies were conducted in 2022 and 2023 near Rocky Mount and Clayton, NC, to determine the optimal granular ammonium sulfate (AMS) rate and application timing for pyroxasulfone-coated AMS. In the rate study, AMS rates included 161, 214, 267, 321, 374, 428, and 481 kg ha-1, equivalent to 34, 45, 56, 67, 79, 90, and 101 kg N ha-1, respectively. All rates were coated with pyroxasulfone at 118 g ai ha-1 and top-dressed onto 5- to 7-leaf cotton. In the timing study, pyroxasulfone (118 g ai ha-1) was coated on AMS and top-dressed at 321 kg ha-1 (67 kg N ha-1) onto 5- to 7-leaf, 9- to 11-leaf, and first bloom cotton. In both studies, weed control and cotton tolerance to pyroxasulfone-coated AMS was compared to pyroxasulfone applied postemergence (POST) and postemergence-directed (POST-directed). The check in both studies received non-herbicide-treated AMS (321 kg ha-1). Before treatment applications, all plots (including the check) were maintained weed-free with glyphosate and glufosinate. In both studies, pyroxasulfone applied POST was most injurious (8 to 16%), while pyroxasulfone-coated AMS resulted in ≤ 4% injury. Additionally, no differences in cotton lint yield were observed in both studies. With the exception of the lowest rate of AMS (161 kg ha-1; 79%), all AMS rates coated with pyroxasulfone controlled Palmer amaranth ≥ 83%, comparable to pyroxasulfone applied POST (92%) and POST-directed (89%). In the timing study, the application method did not affect Palmer amaranth control; however, applications made at the mid- and late timings outperformed early applications. These results indicate pyroxasulfone-coated AMS can control Palmer amaranth comparable to pyroxasulfone applied POST and POST-directed, with minimal risk of cotton injury. However, the application timing could warrant additional treatment to achieve adequate late-season weed control.

Biosimilars in pediatric rheumatology: innovations, challenges, and opportunities.

Biosimilars are biologic medications designed to closely replicate the properties of previously approved biologic disease-modifying anti-rheumatic drugs (bDMARDs). They offer a cost-effective alternative once the original product's patent has expired. In pediatric rheumatology, the use of biosimilars began in 2013 with the launch of the infliximab biosimilar. Since then, more biosimilars, including etanercept, rituximab, and adalimumab, have been introduced, providing additional treatment options for children with rheumatic diseases. This article explores the role of biosimilars in pediatric rheumatology, particularly in juvenile idiopathic arthritis, focusing on their development, safety, and efficacy, as well as the challenges associated with their clinical adoption. It also addresses the importance of education in improving understanding of biosimilars. The article provides insights into their safety, effectiveness, and economic impact by reviewing current literature to help healthcare professionals make informed decisions for treating pediatric rheumatic diseases. Education for both patients and healthcare providers, effective communication, and expectation management play a critical role in ensuring appropriate treatment continuity.

4.5-Year Follow-up with a Novel Corneal Endothelial Prosthesis.

Refractory corneal edema is the foremost reason for endothelial corneal transplantation (EK) in the world. Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) offer good clinical outcomes. However, human donor tissue is limited in availability and has a complex logistical chain. Many patients in need do not have access to EK. Success of the human donor tissue depends on its quality, the number of rebubbles, repeat keratoplasties, and patient-related risk factors. The use of an endothelial corneal keratoprosthesis could benefit patients with a high risk for graft failure and human graft rejection, and patients in underserved areas where tissue banking is unavailable. Case cohort series of 10 eyes of 10 patients implanted with the EndoArt, with a follow-up of up to 4.5 years. Outcome measures are device adherence, central corneal thickness, visual acuity, and incidence of adverse events. In the first seven eyes, the EndoArt was implanted in eyes with low visual potential within the first-in-human (FIH) trial, and in the three remaining eyes, implantation was performed because of either guarded posterior or anterior segment prognosis or the patient's wishes. In 9/10 eyes, device adherence was obtained and maintained throughout the follow-up period. Mean corneal thickness decreased from 927 + SD 241 microns to 621 + SD 140 microns. In 6/10 eyes, visual acuity improved from a mean preoperative value of logMAR 1.94 + 0.63 to a mean postoperative value of logMAR 0.8 + 0.64. No pathological thinning or corneal metabolic changes were seen. The surgical technique was developed during the follow-up period. The EndoArt provided a stable decrease in central corneal thickness, improved vision in 60% of eyes, and had no device-related adverse events. The EndoArt is an additional treatment modality for special cases like repeat corneal graft failure in the population of the Western world, or as a primary procedure in underserved areas worldwide.

Treatment of Generalized Pustular Psoriasis with Bimekizumab

Generalized pustular psoriasis (GPP) is a rare but serious subtype of pustular psoriasis. In the United States, the IL-36 inhibitor spesolimab is the only medication currently approved for GPP. We describe the longitudinal treatment of a patient with concomitant GPP, plaque psoriasis, and psoriatic arthritis. After almost a decade of recalcitrant disease and difficulty managing cardiovascular concerns, the patient was successfully treated with bimekizumab, a novel biologic targeting IL-17A/F. To our knowledge, this represents the first case of concomitant GPP and plaque psoriasis treated with this immunomodulator, offering additional treatment options for patients with this challenging disease.

Prognosis of aggressive adult T-cell leukemia/lymphoma with central nervous system infiltration and utility of CD7 versus CADM1 flowcytometric plots of cerebrospinal fluid.

The prognosis of adult T-cell leukemia/lymphoma (ATL) with primary central nervous system (CNS) involvement has been unclear since the advent of new therapies. Recently, we have shown that flow cytometric CD7/CADM1 analysis of CD4 + cells (HAS-Flow) is useful to detect ATL cells that are not morphologically diagnosed as ATL cells. We investigated the role of CNS involvement in ATLusingcytology and HAS-Flow by analyzing cerebrospinal fluid (CSF) from 73 aggressive ATL cases. Based on the findings in CSF, the study subjects were classified into CNS + (cytologically malignant, n = 18), CNS- (cytologically non-malignant and ATL cell population negative in HAS-Flow, n = 44), and CNS-Micro (cytologically non-malignant and ATL cell population positive in HAS-Flow, n = 11) groups. As expected, the CNS + group had a shorter overall survival than the CNS- groups (P < 0.001). However, the CNS-Micro groupshowed no adverse impact on overall survival compared to the CNS- group (P = 0.506),even without additional CNS-targeted treatments. HAS-Flow also demonstrated clinical utility in the diagnosis of CSF lesions in ATL patients with cerebral white matter lesions and in the detection of ATL cells on post-treatment CSF examination in patients with CNS involvement. Our study demonstrates that ATL with CNS involvement have a poor prognosis and that CSF HAS-Flow is useful to assist in the diagnosis of suspected CNS involvement and to detect ATL cells with high sensitivity after treatment.

Comparing Efficacy of Steroid Irrigation + Steroid-eluting Sinus Stent Versus Steroid Irrigation Alone for Maintaining Frontal Sinus Patency After Sinus Surgery: A Randomized Controlled Trial.

Steroid rinses and steroid-eluting stents are both options for preventing postoperative stenosis after frontal sinus surgery. This study aimed to assess whether steroid-eluting stents offer added benefit over steroid rinses alone in postoperative healing and long-term frontal sinus patency. A randomized controlled trial enrolled patients with CRS with nasal polyps (CRSwNP) who underwent surgery for bilateral and equal frontal sinusitis after failing prior medical therapy. Each patient served as their own control, with each patient randomized to stent placement in either right or left frontal sinuses. Exclusion criteria included unequal frontal sinusitis, aspirin exacerbated respiratory disease, cystic fibrosis, primary ciliary dyskinesia, and immunocompromise. All patients used steroid rinses postoperatively. Scarring, edema, patency, and the need for additional treatments were assessed at 1, 3, 12, and 24 weeks postoperatively. Univariate and multivariate analyses were performed. Sixty-two patients were enrolled. Postoperatively, scarring, edema, patency, and the need for further treatment were similar in both groups at 24 weeks (p = 0.878, 0.688, 0.817, 1.00, and 1.00, respectively). Multivariable regression analysis identified time as an independent risk factor for scarring (OR = 1.32, [1.03‒1.71]) and patency (OR = 1.39, [1.10‒1.82]), while it was an independent protective factor for edema (OR = 0.40, [0.32‒0.49]). The steroid-eluting stent did not significantly affect this. For CRSwNP, with or without asthma, without other underlying systemic disease factors, steroid-eluting stents may not add benefit over steroid rinses in reducing postoperative scarring and edema, improving long-term frontal sinus patency, or reducing the need for additional treatments, as long as patients continue topical therapy and know how to rinse effectively.

A Timoshenko–Ehrenfest planar beam element for geometrically nonlinear analysis using rational Bézier representations with varying weights

This study presents an enhanced Timoshenko–Ehrenfest beam element designed for geometrically nonlinear analysis of planar straight beams subjected to small strains. The methodology adopts the isogeometric analysis (IGA) approach, utilizing rational cubic Bernstein basis functions to construct the interpolations of kinematic unknowns. However, in contrast to the traditional IGA concept, the isoparameterization between the reference geometry and kinematic unknowns is relaxed by treating specific weights in the basis functions as degrees of freedom. This approach significantly improves the accuracy of interpolations, providing superior descriptions of complex deformed configurations with only a minimal increase in element degrees of freedom. Notably, the proposed beam element is shown to be free from the locking phenomena, i.e., membrane and shear locking, without the need for additional treatments. Through rigorous numerical experiments, the study demonstrates the exceptional efficiency and robustness of the proposed beam element, confirming its superior capabilities.

Cost-Effectiveness Analysis of Family-Based Treatment With Additional Home Treatment for Adolescent Anorexia Nervosa.

Family-based treatment (FBT) is promising for treating adolescents with anorexia nervosa, but long-term remission rates are modest. Home treatment (HT) as a supplement to FBT aims to enhance sustainability and effectiveness by supporting recovery within the family. This study compares the cost-effectiveness of FBT alone versus FBT with additional HT for adolescents with anorexia nervosa. This cost-effectiveness analysis is based on a non-randomized pilot study, which examined the effectiveness of HT for adolescents with anorexia nervosa, disregarding the financial aspects. HT involved therapeutic interventions delivered in the patient's home environment, while FBT involved structured therapy sessions at the psychiatric clinic. Data from 61 patients were analysed, with 40 receiving FBT+HT and 21 receiving FBT only. Costs included FBT sessions, HT sessions, and inpatient treatment. Effectiveness was measured by weight restoration at thresholds of expected body weight (EBW)>85% and EBW>95%. FBT+HT promoted greater weight restoration within three months compared to FBT alone (70% vs. 52% at EBW>85%; 38% vs. 29% at EBW>95%). FBT+HT was more cost-effective, with lower average costs per patient meeting weight restoration criteria (8243 vs. 20,446 Swiss francs at EBW>85%; 15,387 vs. 37,485 Swiss francs at EBW>95%). Inpatient treatment accounted for most of the cost, with FBT+HT reducing hospitalisation needs. FBT with additional HT is a more cost-effective treatment for adolescents with anorexia nervosa. Although the cost-effectiveness index was relatively high, effective treatment could reduce the long-term burdens of this disorder. Larger long-term studies are needed to validate these findings and assess sustained cost-effectiveness.

Trajectories of Change, Illness Understanding, and Parental Worries in Children and Adolescents Undergoing Internet-Delivered Cognitive-Behavioral Therapy for Functional Abdominal Pain Disorders: Protocol for a Single-Case Design and Explorative Pilot Study.

Functional abdominal pain disorders (FAPDs) are common in young people and are characterized by persistent or recurrent abdominal symptoms without apparent structural or biochemical abnormalities. FAPDs are associated with diminished quality of life, school absence, increased health care use, and comorbid anxiety and depression. Exposure-based internet-delivered cognitive behavioral therapy (ICBT) has demonstrated efficacy in alleviating abdominal symptoms and improving quality of life. However, a deeper understanding of effect mechanisms and identification of possible additional treatment targets could refine treatment. This protocol paper aims to describe a study focusing on children and adolescents undergoing ICBT for FAPDs, aiming to further investigate the underlying mechanisms of effect. Children (8-12 years), adolescents (13-17 years) with FAPDs, and their respective parents will be included for 10 weeks for ICBT. First, detailed trajectories of effect are examined through a randomized single-case design study involving 6 children and 6 adolescents (substudy 1). Following this, an open-ended explorative pilot study with 30 children and 30 adolescents explores potential illness-related cognitive biases and interoceptive accuracy before and after treatment (substudy 2). Finally, spanning across these 2 substudies, including all parents from substudies 1 and 2, we will assess parental distress and illness worries before and after treatment, and how these factors impact the treatment adherence and outcomes of the child or adolescent (substudy 3). Recruitment of participants began in June 2022 and is finalized for substudy 1 and ongoing for substudies 2 and 3. Recruitment is expected to be completed by January 2025, with final data collection during April 2025. The findings have the potential to contribute to the ongoing improvement of specialized psychological treatment for FAPDs in young people. ClinicalTrials.gov NCT05237882; https://clinicaltrials.gov/study/NCT05237882; ClinicalTrials.gov NCT05486585; https://clinicaltrials.gov/study/NCT05486585; OSF Registries osf.io/c49k7; https://osf.io/c49k7. DERR1-10.2196/58563.

Exploiting the fitness cost of metallo-β-lactamase expression can overcome antibiotic resistance in bacterial pathogens.

Carbapenems are last-resort antibiotics for treating bacterial infections. The widespread acquisition of metallo-β-lactamases, such as VIM-2, contributes to the emergence of carbapenem-resistant pathogens, and currently, no metallo-β-lactamase inhibitors are available in the clinic. Here we show that bacteria expressing VIM-2 have impaired growth in zinc-deprived environments, including human serum and murine infection models. Using transcriptomic, genomic and chemical probes, we identified molecular pathways critical for VIM-2 expression under zinc limitation. In particular, disruption of envelope stress response pathways reduced the growth of VIM-2-expressing bacteria in vitro and in vivo. Furthermore, we showed that VIM-2 expression disrupts the integrity of the outer membrane, rendering VIM-2-expressing bacteria more susceptible to azithromycin. Using a systemic murine infection model, we showed azithromycin's therapeutic potential against VIM-2-expressing pathogens. In all, our findings provide a framework to exploit the fitness trade-offs of resistance, potentially accelerating the discovery of additional treatments for infections caused by multidrug-resistant bacteria.