Prefoldin 6 mediates longevity response from heat shock factor 1 to FOXO in C. elegans.

Heat shock factor 1 (HSF-1) and forkhead box O (FOXO) are key transcription factors that protect cells from various stresses. In Caenorhabditis elegans, HSF-1 and FOXO together promote a long life span when insulin/IGF-1 signaling (IIS) is reduced. However, it remains poorly understood how HSF-1 and FOXO cooperate to confer IIS-mediated longevity. Here, we show that prefoldin 6 (PFD-6), a component of the molecular chaperone prefoldin-like complex, relays longevity response from HSF-1 to FOXO under reduced IIS. We found that PFD-6 was specifically required for reduced IIS-mediated longevity by acting in the intestine and hypodermis. We showed that HSF-1 increased the levels of PFD-6 proteins, which in turn directly bound FOXO and enhanced its transcriptional activity. Our work suggests that the prefoldin-like chaperone complex mediates longevity response from HSF-1 to FOXO to increase the life span in animals with reduced IIS.

Medicines and other factors causing deaths in English and welsh care homes: five-years of preventing future death reports by coroners.

BACKGROUND: Whilst information has been published on the impact, severity and causes of incidents involving medicines in care homes, it has not been systematically described. This review explored whether coroners' Preventing Future Death (PFD) reports involving medicines for people living in care homes could add to this evidence base. METHODS: PFD reports made publicly available between 2017 and 2021 classified as 'care home-related deaths' were reviewed. Reports describing medicines and/or medicines processes were identified. Contributory factors within these reports were then identified. RESULTS: Within the timeframe, 156 reports were published, and 25 described medicines (n = 27) or medicines processes (n = 5) concerning people living in care homes. The impact of medicines and/or medicines processes was quantified as no impact (n = 7), contributory (n = 6) and direct (n = 14) per report. Two key themes emerged. Four deaths had an association between their falls risk, prescribed anticoagulants, and the failure of the service to seek timely emergency care following a fall and two deaths concerned endocrine medicines, where people refused insulin or blood sugar monitoring and staff did not seek timely advice. CONCLUSION: This study demonstrated PFD reports provide an insight into the potential association between medicines, and other aspects of the person's care in causing harm.

Care needs and self-induced measures of women with postpartum pelvic floor disorder- Results of a social media-based survey of 2930 women.

INTRODUCTION: Pelvic floor disorders (PFD) occur in about 40% of women after delivery. Less is known about the intervention and care needs of women with postpartum PFD. The aim of this analysis was to analyze care needs and self-initiated measures to strengthen the pelvic floor in postpartum women in relation to incontinence and sexual dysfunction. Furthermore, influencing factors for self-initiated measures were evaluated. PATIENTS AND METHODS: An anonymous online survey (via LimeSurvey) was conducted between September and October 2022 and distributed via social media (Instagram and Facebook). The survey explicitly addressed mothers with and without pelvic floor disorders up to 5 years postpartum (inclusion criteria). Validated instruments were employed to assess incontinence (ICIQ-SF) and sexual functioning (PISQ-IR: Condition Impact). The questions on the use of services and preventive measures, as well as on the interaction with a gynecologist, were based on self-developed items. RESULTS: In total, 49.4% of the participants of the survey showed symptoms of urinary incontinence (UI). Furthermore, only 40.3% (n = 241) of women were actively asked by their gynecologists for the occurrence of UI or PFD among those who suffered from PFD. Overall, 79.3% of the participants of the survey with UI underwent measures to deal with the complaints. The ICIQ-SF Score was significantly associated with all self-induced measures. High School diplomas and academic degrees were associated with the use of love balls (p < 0.05). CONCLUSION: The results of the study show the unmet needs of postpartum women. PFD should be addressed more frequently in the outpatient setting. Furthermore, more systematic information about the treatment of PFD could help to address unmet information needs and improve interventions.

Prefoldin 2 contributes to mitochondrial morphology and function.

BACKGROUND: Prefoldin is an evolutionarily conserved co-chaperone of the tailless complex polypeptide 1 ring complex (TRiC)/chaperonin containing tailless complex 1 (CCT). The prefoldin complex consists of six subunits that are known to transfer newly produced cytoskeletal proteins to TRiC/CCT for folding polypeptides. Prefoldin function was recently linked to the maintenance of protein homeostasis, suggesting a more general function of the co-chaperone during cellular stress conditions. Prefoldin acts in an adenosine triphosphate (ATP)-independent manner, making it a suitable candidate to operate during stress conditions, such as mitochondrial dysfunction. Mitochondrial function depends on the production of mitochondrial proteins in the cytosol. Mechanisms that sustain cytosolic protein homeostasis are vital for the quality control of proteins destined for the organelle and such mechanisms among others include chaperones. RESULTS: We analyzed consequences of the loss of prefoldin subunits on the cell proliferation and survival of Saccharomyces cerevisiae upon exposure to various cellular stress conditions. We found that prefoldin subunits support cell growth under heat stress. Moreover, prefoldin facilitates the growth of cells under respiratory growth conditions. We showed that mitochondrial morphology and abundance of some respiratory chain complexes was supported by the prefoldin 2 (Pfd2/Gim4) subunit. We also found that Pfd2 interacts with Tom70, a receptor of mitochondrial precursor proteins that are targeted into mitochondria. CONCLUSIONS: Our findings link the cytosolic prefoldin complex to mitochondrial function. Loss of the prefoldin complex subunit Pfd2 results in adaptive cellular responses on the proteome level under physiological conditions suggesting a continuous need of Pfd2 for maintenance of cellular homeostasis. Within this framework, Pfd2 might support mitochondrial function directly as part of the cytosolic quality control system of mitochondrial proteins or indirectly as a component of the protein homeostasis network.

Pelvic Floor Physical Therapy and Its Merit in the Treatment of Female Urogenital Pain.

PURPOSE OF REVIEW: Female urogenital pain (FUGP) affects many women and is often a diagnosis of exclusion. The long path to a diagnosis and subsequent treatment frequently leads to suffering on the individual's behalf (Obstet. Gynecol. 121: 645-50, 2013). Additionally, this delay in diagnosis and thus treatment places stress on the US medical system (Obstet. Gynecol. 121: 645-50, 2013). There is a lack of knowledge regarding the scope of pelvic floor physical therapy (PFPT) across the medical community that may prevent physicians from referring patients (J Urol. 193:1545-53, 2015; Sex Med Rev., 2021). PFPT is a low-risk, potentially high-reward option that should be recognized as part of the multidisciplinary approach to managing FUGP. RECENT FINDINGS: Research databases (PubMed and Cochrane) were used to find articles on FUGP between 2005 and 2022. Systematic reviews, randomized controlled trials (RCTs), prospective and retrospective cohorts, and case-study analyses were included in reviewing the literature. The most recent studies in the last 2 years show the benefit of PFPT in certain FUGP diagnoses with improved pain scores and function when compared to no intervention or placebo treatment. The aim of this article is to elucidate the scope of PFPT in the treatment of FUGP with supporting research findings regarding efficacy. It is clear from the literature that PFPT should be recognized by referring physicians as part of a multidisciplinary approach to the treatment of FUGP.

The unconventional prefoldin RPB5 interactor mediates the gravitropic response by modulating cytoskeleton organization and auxin transport in Arabidopsis.

Gravity-induced root curvature involves the asymmetric distribution of the phytohormone auxin. This response depends on the concerted activities of the auxin transporters such as PIN-FORMED (PIN) proteins for auxin efflux and AUXIN RESISTANT 1 (AUX1) for auxin influx. However, how the auxin gradient is established remains elusive. Here we identified a new mutant with a short root, strong auxin distribution in the lateral root cap and an impaired gravitropic response. The causal gene encoded an Arabidopsis homolog of the human unconventional prefoldin RPB5 interactor (URI). AtURI interacted with prefoldin 2 (PFD2) and PFD6, two ß-type PFD members that modulate actin and tubulin patterning in roots. The auxin reporter DR5rev :GFP showed that asymmetric auxin redistribution after gravistimulation is disordered in aturi-1 root tips. Treatment with the endomembrane protein trafficking inhibitor brefeldin A indicated that recycling of the auxin transporter PIN2 is disrupted in aturi-1 roots as well as in pfd mutants. We propose that AtURI cooperates with PFDs to recycle PIN2 and modulate auxin distribution.

The prevalence of frailty and post-treatment outcomes in elderly women with pelvic floor disorders.

INTRODUCTION AND HYPOTHESIS: Women seeking treatment for pelvic floor disorders (PFD) may have a high prevalence of frailty, which could potentially impact the risks of treatment. The present study was aimed to assess the prevalence of frailty in patients with PFD and additionally to compare post-treatment complications between frail and non-frail patients. METHODS: This is a prospective observational study conducted in a single secondary referral centre for PFD. Women with PFD and aged ≥ 65 years were eligible for inclusion. Frailty was classified using a validated screening tool, the Groningen Frailty Indicator (GFI). The primary outcome was to determine the prevalence of frailty in elderly women with symptoms of pelvic floor disorders. Secondary outcomes were clinical outcomes after treatment between frail and non-frail patients. RESULTS: A total of 263 women were included. The prevalence of frailty was 54.4% (143 women, 95% CI 48.1-60.5) in the studied group of patients. Frail patients had more comorbidities and used more medication compared to non-frail patients. Non-frail patients were more often surgically treated than frail patients. No differences were found in the incidence of postoperative complications. CONCLUSIONS: Our study shows a high prevalence of frailty in elderly women with symptoms of PFD. Further research is required to investigate whether these frail patients face an increased risk of complications and poor clinical outcomes after treatment for PFD.

Posterior fossa decompression with or without duraplasty for patients with chiari type I malformation and basilar impression: a meta-analysis.

BACKGROUND: To compare clinical effect and safety between posterior fossa decompression with duraplasty (PFDD) and posterior fossa decompression without duraplasty (PFD) in treatment of Chiari type I malformation and basilar impression. METHODS: A comprehensive computer search was conducted from 2000 to 2019. The quality assessment was performed by the QUADAS-2 tool. The clinical value of comparison between PFDD and PFD was evaluated by using the pooled estimate of sensitivity and specificity. In addition, sensitivity analysis and bias analysis were applied to ensure the accuracy of the results. RESULTS: Finally, 468 patients were enrolled in 6 studies and ultimately met the eligibility criteria. The PFDD and PFD groups were 282 and 186, respectively. The meta-analysis showed no significant difference in the Chicago Chiari Outcome Scale (COSS score) (MD = 0.14, 95% CI [-0.23, 0.50], P = 0.47; P = heterogeneity = 0.86, I2 = 0%). Meanwhile, Significant difference existed in length of stay (MD = -1.08, 95% CI [-1.32, -0.84], P = 0.001; heterogeneity P < 0.000001, I2 = 85%) and complications (OR = 0.35, 95%CI [0.20, 0.62], P = 0.0003; P for Heterogeneity = 0.04, I2 = 56%). CONCLUSION: PFD is a more efficient and safer therapy than PFDD in the treatment of Chiari type I malformation with basilar impression.

Comparative Evaluation of 15 Laser and Perfluorodecalin Combinations for Tattoo Removal.

BACKGROUND AND OBJECTIVES: We present a case of laser tattoo removal treated with 15 different combinations using picosecond 1064 nm, picosecond 755 nm, nanosecond 755 nm, and a fractionated CO2 laser, both with and without a perfluorodecalin (PFD) patch to ascertain the most effective approach. STUDY DESIGN/MATERIALS AND METHODS: A single lower extremity black tattoo was divided into 15 treatment sections allowing for testing of various laser and PFD combinations. Sectioned treatment was conducted until a treatment superiority was noted. RESULTS: After two sessions using sectioned combination treatments with a 4-week interval clinically significant results were produced. CONCLUSIONS: The combination of picosecond 1064 nm, picosecond 755 nm, and a fractionated CO2 laser without the PFD patch showed superior clinical improvement over the other combinations. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

The effect of the perfluorodecalin patch on particle emission and skin temperature during laser-induced tattoo removal.

Laser-based procedures for tattoo removals are popular due to high efficacy and a relatively moderate insult. However, it often requires multiple sessions to achieve a satisfactory effect. The perfluorodecalin (PFD) patch utilizes an optical clearing agent to speed up the removal process and may decrease skin insult and harmful particles emission during treatment. This study assessed in pigs the effect of the PFD patch in connection with laser treatment of skin with and without tattoos to determine whether the PFD patch provides benefit in lowering thermal skin insult and particle emission during treatment. Skin temperature measured by infrared thermometer during laser treatment or shortly thereafter showed a significant (approximately 40%) decrease with the PFD patch in sites with tattoos. For laser-treated sites without tattoos, there was a significant decrease of particles observed with the PFD patch. In laser-treated sites with tattoos, a strong trend was seen (approximately a twofold decrease) but did not reach statistical significance due to high variability. The present data show that the PFD patch limits the increase in skin temperature produced with laser during treatment. Moreover, it decreases the emission of particles in sites without tattoos and is suggestive of a similar effect in sites with tattoos.

The Non-Bone-Related Role of RANK/RANKL Signaling in Cancer.

RANK ligand (RANKL) is a member of the tumor necrosis factor alpha superfamily of cytokines. It is the only known ligand binding to a membrane receptor named receptor activator of nuclear factor-kappa B (RANK), thereby triggering recruitment of TNF receptor-associated factor (TRAF) adaptor proteins and activation of downstream pathways. RANK/RANKL signaling is controlled by a decoy receptor, osteoprotegerin (OPG), but also has additional more complex levels of regulation. It is crucial for the differentiation of bone-resorbing osteoclasts and is deregulated in disease processes such as osteoporosis and cancer bone metastasis. Cells expressing RANK and RANKL are commonly found in the tumor environment. In many tumor types, the RANK/RANKL pathway is overexpressed, and this is in most cases correlated with poor prognosis. RANK signaling plays an important role in the innate and adaptive immune response, generates regulatory T (Treg) cells, and increases the production of cytokines. It is also involved in chemo resistance in vitro. Recent evidence suggests that RANKL blockade improves the efficacy of anti-CTLA-4 antibodies against solid tumors and experimental metastasis. Therefore, there is increasing interest to use RANKL inhibition as an immunomodulatory strategy in an attempt to make immune-resistant tumor responsive to immune therapy.

Accelerometers: Assessing their potential for measuring personal flotation device use on commercial fishing vessels.

BACKGROUND: Falls overboard are the most common cause of fatalities in commercial fishing. As a result, interventions aimed at increasing and measuring the use of personal flotation devices (PFDs) are a high priority. The focus of this study was to explore the use of accelerometers as a means for objectively measuring PFD use on lobster fishing vessels. METHODS: For participating vessels, researchers attached an accelerometer to a PFD worn by a crewmember and another to the vessel's wheelhouse. GoPro videos were also employed to record crewmember activities so these could be synchronized with accelerometer outputs. Accelerometer outputs included two distinct measures, the proportional integration mode (PIM) and zero crossing mode (ZCM). Data were fitted to various equations to identify the best method for predicting PFD use. RESULTS: Seven lobster fishing vessels participated in the trial. Data indicated that accelerometers could predict PFD use with a fairly high degree of accuracy. In particular, a logistic equation incorporating PIM values from the PFD and the absolute value of the difference between the PFD PIM readings and the PIM readings from the stationary accelerometer demonstrated the highest degree of accuracy, with correct classifications for 73.3% to 77.6% of the 10-second data intervals. Accuracy was highest when crew members were moving versus stationary. The predictive value of ZCM was comparatively limited. CONCLUSIONS: PIM accelerometer readings can be used to measure PFD use with a considerably high degree of accuracy, especially for sternmen who are moving regularly and have the highest risk for falling overboard.

Reviewing the prognostic factors in myelomeningocele.

OBJECTIVE: The goal of this study was to analyze the factors that have an impact on morbidity and mortality in patients with myelomeningocele (MMC). METHODS: A retrospective cohort study was conducted to analyze factors associated with MMC that influence the morbidity and mortality of the disease. Data were collected from medical records of children who underwent the primary repair of MMC at the Fernandes Figueira Institute-Oswaldo Cruz Foundation (IFF-Fiocruz) between January 1995 and January 2015, with a minimum follow-up of 1 year. The following variables were analyzed: demographic characteristics (gestational age, sex, and birth weight); clinical features (head circumference at birth, anatomical and functional levels of MMC, hydrocephalus, symptomatic Chiari malformation type II, neurogenic bladder, and urinary tract infection [UTI]); and surgical details such as timing of repair of MMC, age at first shunt placement, shunt surgery modality (elective or emergency), concurrent surgery (correction of MMC and shunt insertion in the same surgical procedure), incidence and cause of shunt dysfunction, use of external ventricular drain, transfontanelle puncture, surgical wound complications prior to shunting, and endoscopic treatment of hydrocephalus. RESULTS: A total of 231 patients with MMC were included in the analysis. Patients were followed for periods ranging from 1 to 20 years, with a mean of 6.9 years. The frequency of shunt placement was observed mainly among patients with MMC at the highest spinal levels (p < 0.01). The main causes of morbidity and mortality in patients with MMC were shunt failures, diagnosed in 91 of 193 cases (47.2%) of hydrocephalus, and repeated UTIs, in 129 of 231 cases (55.8%) of MMC; these were the main causes of hospitalization and death. Head circumference ≥ 38 cm at birth was found to be a significant risk factor for shunt revision (p < 0.001; 95% CI 1.092-1.354). Also, the lumbar functional level of MMC was associated with less revision than upper levels (p < 0.014; 95% CI 0.143-0.805). There was a significant association between recurrent UTI and thoracic functional level. CONCLUSIONS: Macrocephaly at birth and higher levels of the defect have an impact on worse outcome and, therefore, are a challenge to the daily practice of pediatric neurosurgery.

Evaluation of a transparent perfluorodecalin-infused patch as an adjunct to laser-assisted tattoo removal: A pivotal trial.

BACKGROUND AND OBJECTIVE: Laser-assisted treatment of tattoos is well recognized to produce opaque epidermal whitening that prevents multiple sequential passes during a single treatment session. The amount of epidermal whitening produced in association with the procedure can be minimized by topical application of perfluorodecalin (PFD), which is an optical clearing agent. This pivotal trial assessed the ability of a transparent PFD-infused patch used in conjunction with a Q-switched nanosecond laser in the treatment of tattoos to permit multiple laser passes during a single 5 minute treatment session in comparison to the number of passes that could be completed using conventional treatment of the tattoo with the laser alone. STUDY DESIGN: Thirty subjects (mean age 37 years; 14 males) with predominantly dark blue or black tattoos were enrolled in a split-tattoo trial. One half of each tattoo was treated conventionally, whereas the other half was treated through the PFD patch. Treatments were performed using a nanosecond Q-switched 755-nm Alexandrite laser. The number of treatments performed in a 5-minute time period was quantified for each side of the tattoo (primary effectiveness outcome). Patient-reported pain scores and adverse events (AEs) were also evaluated. RESULTS: Significantly more laser passes could be made on average using the PFD patch compared with treatment using the laser alone (3.7 passes vs. 1.4 passes; P < 0.001). AEs were limited to those expected during laser removal of tattoos. The proportions of subjects with transient edema and erythema were lower in the PFD patch treatment group (36.7% vs. 63.3% and 33.3% vs. 70.0%, respectively); all AEs were transient and resolved quickly. No patient in either group exhibited dyschromia (hypo- or hyperpigmentation) in the treatment area at the 1-month post treatment visit. Additionally, when surveyed at the 1-month follow-up visit, all subjects (30/30) preferred to continue laser-assisted tattoo removal with the PFD patch. CONCLUSION: An average of 3.7 laser passes were made in a defined 5-minute treatment session when using the transparent PFD-infused patch, which is significantly more than was possible with the laser alone (average of 1.4 passes). Use of the PFD patch was associated with improved tolerability compared with conventional treatment, with subjects experiencing fewer and less severe AEs related to epidermal injury. Lasers Surg. Med. 49:335-340, 2017. © 2017 Wiley Periodicals, Inc.

Chiari-related hydrocephalus: assessment of clinical risk factors in a cohort of 297 consecutive patients.

OBJECTIVE Patients treated for Chiari I malformation (CM-I) with posterior fossa decompression (PFD) may occasionally and unpredictably develop postoperative hydrocephalus. The clinical risk factors predictive of this type of Chiari-related hydrocephalus (CRH) are unknown. The authors' objective was to evaluate their experience to identify risk factors that may predict which of these patients undergoing PFD will develop CRH after surgery. METHODS The authors performed a retrospective clinical chart review of all patients who underwent PFD surgery and duraplasty for CM-I at the Primary Children's Hospital in Utah from June 1, 2005, through May 31, 2015. Patients were dichotomized based on the need for long-term CSF diversion after PFD. Analysis included both univariate and multivariable logistic regression analyses. RESULTS The authors identified 297 decompressive surgeries over the period of the study, 22 of which required long-term postoperative CSF diversion. On multivariable analysis, age < 6 years old (OR 3.342, 95% CI 1.282-8.713), higher intraoperative blood loss (OR 1.003, 95% CI 1.001-1.006), and the presence of a fourth ventricular web (OR 3.752, 95% CI 1.306-10.783) were significantly associated with the need for long-term CSF diversion after decompressive surgery. CONCLUSIONS Younger patients, those with extensive intraoperative blood loss, and those found during surgery to have a fourth ventricular web were at higher risk for the development of CRH. Clinicians should be alert to evidence of CRH in this patient population after PFD surgery.

Action spectra of photosystems II and I and quantum yield of photosynthesis in leaves in State 1.

The spectral global quantum yield (YII, electrons/photons absorbed) of photosystem II (PSII) was measured in sunflower leaves in State 1 using monochromatic light. The global quantum yield of PSI (YI) was measured using low-intensity monochromatic light flashes and the associated transmittance change at 810nm. The 810-nm signal change was calibrated based on the number of electrons generated by PSII during the flash (4·O2 evolution) which arrived at the PSI donor side after a delay of 2ms. The intrinsic quantum yield of PSI (yI, electrons per photon absorbed by PSI) was measured at 712nm, where photon absorption by PSII was small. The results were used to resolve the individual spectra of the excitation partitioning coefficients between PSI (aI) and PSII (aII) in leaves. For comparison, pigment-protein complexes for PSII and PSI were isolated, separated by sucrose density ultracentrifugation, and their optical density was measured. A good correlation was obtained for the spectral excitation partitioning coefficients measured by these different methods. The intrinsic yield of PSI was high (yI=0.88), but it absorbed only about 1/3 of quanta; consequently, about 2/3 of quanta were absorbed by PSII, but processed with the low intrinsic yield yII=0.63. In PSII, the quantum yield of charge separation was 0.89 as detected by variable fluorescence Fv/Fm, but 29% of separated charges recombined (Laisk A, Eichelmann H and Oja V, Photosynth. Res. 113, 145-155). At wavelengths less than 580nm about 30% of excitation is absorbed by pigments poorly connected to either photosystem, most likely carotenoids bound in pigment-protein complexes.

Rapid, high-fluence multi-pass q-switched laser treatment of tattoos with a transparent perfluorodecalin-infused patch: A pilot study.

BACKGROUND AND OBJECTIVES: Perfluorodecalin (PFD) has previously been shown to rapidly dissipate the opaque, white micro-bubble layer formed after exposure of tattoos to Q-switched lasers [1]. The current pilot study was conducted to qualitatively determine if the use of a transparent PFD-infused silicone patch would result in more rapid clearance of tattoos than conventional through-air techniques. MATERIALS AND METHODS: Black or dark blue tattoos were divided into two halves in a single-site IRB-approved study with 17 subjects with Fitzpatrick skin types I-III. One half of each tattoo served as its own control and was treated with one pass of a standard Q-switched Alexandrite laser (755 nm). The other half of the tattoo was treated directly through a transparent perfluorodecalin (PFD) infused patch (ON Light Sciences, Dublin, CA). The rapid whitening reduction effect of the Patch routinely allowed three to four laser passes in a total of approximately 5 minutes. Both sides were treated at highest tolerated fluence, but the optical clearing, index-matching, and epidermal protection properties of the PFD Patch allowed significantly higher fluence compared to the control side. Standard photographs were taken at baseline, immediately prior to treatment with the PFD Patch in place, and finally before and after each treatment session. Treatments were administered at 4- to 6-week intervals. RESULTS: In a majority of subjects (11 of 17), tattoos treated through a transparent PFD-infused patch showed more rapid tattoo clearance with higher patient and clinician satisfaction than conventional treatment. In no case did the control side fade faster than the PFD Patch side. No unanticipated adverse events were observed. CONCLUSIONS: Rapid multi-pass treatment of tattoos with highest tolerated fluence facilitated by a transparent PFD-infused patch clears tattoos more rapidly than conventional methods.

Strong alkalinization of Chara cell surface in the area of cell wall incision as an early event in mechanoperception.

Mechanical wounding of cell walls occurring in plants under the impact of pathogens or herbivores can be mimicked by cell wall incision with a glass micropipette. Measurements of pH at the surface of Chara corallina internodes following microperforation of cell wall revealed a rapid (10-30s) localized alkalinization of the apoplast after a lag period of 10-20s. The pH increase induced by incision could be as large as 3 pH units and relaxed slowly, with a halftime up to 20min. The axial pH profile around the incision zone was bell-shaped and localized to a small area, extending over a distance of about 100µm. The pH response was suppressed by lowering cell turgor upon the replacement of artificial pond water (APW) with APW containing 50mM sorbitol. Stretching of the plasma membrane during its impression into the cell wall defect is likely to activate the Ca(2+) channels, as evidenced from sensitivity of the incision-induced alkalinization to the external calcium concentration and to the addition of Ca(2+)-channel blockers, such as La(3+), Gd(3+), and Zn(2+). The maximal pH values attained at the incision site (~10.0) were close to pH in light-dependent alkaline zones of Chara cells. The involvement of cytoskeleton in the origin of alkaline patch was documented by observations that the incision-induced pH transients were suppressed by the inhibitors of microtubules (oryzalin and taxol) and, to a lesser extent, by the actin inhibitor (cytochalasin B). The results indicate that the localized increase in apoplastic pH is an early event in mechanoperception and depends on light, cytoskeleton, and intracellular calcium.

Caregiver training improves child feeding behaviours in children with paediatric feeding disorder and may reduce caregiver stress: A systematic review and meta-analysis.

PURPOSE: The purpose of this systematic review and meta-analysis was to synthesise the evidence from randomised controlled trials for caregiver training on child and family outcomes for children with paediatric feeding disorder. METHOD: A systematic review was conducted in accordance with PRISMA guidelines. Searches of Medline, CINAHL, PsychInfo, and EMBASE were conducted using the key concepts of paediatrics, feeding disorders, parents/caregivers, and training. Eligible studies included randomised controlled trials published in peer-reviewed articles, testing the impact of caregiver training on outcomes for children with paediatric feeding disorder. RESULT: Eight articles met the inclusion criteria, involving 575 participants from three countries. Seven articles were included in the meta-analyses, providing high certainty evidence that caregiver training improves child feeding behaviours and reduces unhelpful caregiver mealtime strategies compared with no intervention. Uncertainty remains in regard to impact on caregiver stress and intervention intensity. CONCLUSION: Caregiver training is an effective strategy for improving outcomes in children with paediatric feeding disorder. Further research is required to determine the most effective methods of caregiver training, including the intensity of treatment required to attain clinically important benefits for families with different levels of need.

Molecular mechanisms of pelvic organ prolapse influenced by FBLN5 via FOSL1/miR-222/MEIS1/COL3A1 axis.

This study delves into the role of FBLN5 in pelvic organ prolapse (POP) and its molecular mechanisms, focusing on the FOSL1/miR-222/MEIS1/COL3A1 axis. Gene relationships linked to POP were confirmed using bioinformatics databases like GEO and StarBase. Primary human uterosacral ligament fibroblasts (hUSLF) were extracted and subjected to mechanical stretching. Cellular cytoskeletal changes were examined via phalloidin staining, intracellular ROS levels with a ROS kit, cell apoptosis through flow cytometry, and cell senescence using ß-galactosidase staining. FBLN5's downstream targets were identified, and the interaction between FOSL1 and miR-222 and miR-222 and MEIS1 were validated using assays. In rat models, the role of FBLN5 in POP was assessed using bladder pressure tests. Results indicated diminished FBLN5 expression in uterine prolapse. Enhanced FBLN5 countered mechanical damage in hUSLF cells by downregulating FOSL1. FOSL1 augmented miR-222, inhibiting MEIS1, which subsequently fostered COL3A1 transcription. In rat models, the absence of FBLN5 exacerbated POP by influencing the FOSL1/miR-222/MEIS1/COL3A1 pathway. FBLN5's protective role likely involves regulating the above axis and boosting COL3A1 expression. Further research is needed to validate the effectiveness and safety of this mechanism in human patients and to propose potential new treatment options.