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Importance: Male postpartum depression is prevalent across populations; however, there is limited evidence on strategies to address it, particularly in low-income settings., Objective: To evaluate the effectiveness of Learning Through Play Plus Dads (LTP + Dads), a nonspecialist-delivered psychosocial intervention, in improving symptoms of male postpartum depression compared to treatment as usual., Design, Setting, and Participants: This cluster randomized clinical trial was conducted in Karachi, Pakistan, between June 2018 and November 2019. Assessors were blind to treatment allocation. Participants were recruited from 2 large towns in the city of Karachi via basic health units. Fathers aged 18 years and older with a DSM-5 diagnosis of major depressive episode and a child younger than 30 months were recruited. Of 1582 fathers approached, 1527 were screened and 357 were randomized in a 1:1 ratio to either the intervention or treatment as usual; 328 were included in the final analysis. Data were analyzed from April to June 2022., Interventions: LTP + Dads is a manualized intervention combining parenting skills training, play therapy, and cognitive behavior therapy. The intervention was delivered by community health workers via 12 group sessions over 4 months., Main Outcomes and Measures: The primary outcome was change in 17-item Hamilton Depression Rating Scale score at 4 months. Secondary outcomes included anxiety symptoms; parenting stress; intimate partner violence; functioning; quality of life; and child social, emotional, and physical health outcomes. Assessments were completed at baseline and 4 and 6 months postrandomization., Results: Of the 357 fathers included (mean [SD] age, 31.44 [7.24] years), 171 were randomized to the intervention and 186 to treatment as usual. Participants randomized to the intervention demonstrated significantly greater improvements in depression (group difference ratio [GDR], 0.66; 95% CI, 0.47 to 0.91; P < .001), anxiety (GDR, 0.62; 95% CI, 0.48 to 0.81; P < .001), parenting stress (GDR, -12.5; 95% CI, -19.1 to -6.0; P < .001), intimate partner violence (GDR, 0.89; 95% CI, 0.80 to 1.00; P = .05), disability (GDR, 0.77; 95% CI, 0.61 to 0.97; P = .03), and health-related quality of life (GDR, 12.7; 95% CI, 0.17 to 0.34; P < .001) at 4 months. The difference in depression and parenting stress was sustained at 6 months. Children of fathers randomized to the parenting intervention had significantly greater improvements in social-emotional development scores (mean difference, -20.8; 95% CI, -28.8 to -12.9; P < .001) at 6 months., Conclusions and Relevance: The psychosocial parenting intervention in this study has the potential to improve paternal mental health and child development in Pakistan. Further studies in other populations and with longer follow-up are warranted., Trial Registration: ClinicalTrials.gov Identifier: NCT03564847.

As attachment-based interventions can improve caregiver-infant relationships and their subsequent psychological outcomes, the identification of relevant and effective interventions can facilitate their implementation into clinical practice. This systematic review aimed to a) provide an overview of manualised attachment-based interventions, without video-feedback as the main component, for caregivers and infants from conception to two years, and b) determine which of these interventions were effective in demonstrating improvements in caregiver-infant relational outcomes. To identify eligible interventions and their empirical evidence base, two search stages were conducted for 1) relevant interventions and 2) studies of interventions identified in the first stage that focussed on caregiver-infant relational outcomes. All studies included in Stage 2 were quality assessed and findings analysed. Twenty-six interventions were eligible for inclusion at Stage 1 but studies reporting on relational outcomes were identified for 16 interventions only. Forty studies reporting on those 16 interventions met inclusion criteria and were synthesised at Stage 2. Most studies were of good quality. Observer-rated measures were used in 90% of studies. There was evidence for these interventions in relation to improving caregiver-infant relational outcomes: 80% of studies reported a statistically significant positive change in a relational outcome for the intervention compared to pre-intervention or control group. The most promising evidence was identified for Attachment and Biobehavioral Catch-Up (ABC), Minding the Baby (MTB) and Circle of Security (COS). This systematic review offers guidance to healthcare professionals, commissioners and policymakers within perinatal sectors in relation to the training, delivery and implementation of evidenced manualised attachment-based interventions., Competing Interests: Declarations Conflict of Interest The authors AW, CC, and MWW declare that they have no competing interests. Whilst MWW and AW have evaluated some parenting interventions in this field, these were not included in this review. Ethical Approval Not applicable. Informed Consent Not applicable., (© 2024. The Author(s).)

Cognitive markers may in theory be more sensitive to the effects of intervention than overt behavioral measures. The current study tests the impact of the Intervention with the British Autism Study of Infant Siblings-Video Interaction for Promoting Positive Parenting (iBASIS-VIPP) on an eye-tracking measure of social attention: dwell time to the referred object in a gaze following task. The original two-site, two-arm, assessor-blinded randomized controlled trial (RCT) of this intervention to increase parental awareness, and responsiveness to their infant, was run with infants who have an elevated familial likelihood for autism (EL). Fifty-four EL infants (28 iBASIS-VIPP intervention, 26 no intervention) were enrolled, and the intervention took place between 9 months (baseline) and 15 months (endpoint), with gaze following behavior measured at 15 months. Secondary intention to treat (ITT) analysis showed that the intervention was associated with significantly reduced dwell time to the referent of another person's gaze (β = -0.32, SE = 0.14, p = 0.03) at 15-month treatment endpoint. Given the established link between gaze following and language, the results are considered in the context of a previously reported, non-significant and transient trend toward lower language scores at the treatment endpoint (Green et al. (2015) The Lancet Psychiatry, 2(2), 133-140). Future intervention trials should aim to include experimental cognitive measures, alongside behavioral measures, to investigate mechanisms associated with intervention effects., (© 2024 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Developmental antecedents of autism may affect parent-infant interactions (PII), altering the context in which core social skills develop. While studies have identified differences in PII between infants with and without elevated likelihood (EL) for autism, samples have been small. Here, we examined whether previously reported differences are replicable. From a longitudinal study of 113 EL and 27 typical likelihood infants (TL), 6-min videotaped unstructured PII was blind rated at 8 and 14 months on eight interactional qualities. Autism outcome was assessed at 36 months. Linear mixed-effects models found higher parent sensitive responsiveness, nondirectiveness, and mutuality ratings in TL than EL infants with and without later autism. PII qualities at 8 (infant positive affect, parent directiveness) and 14 months (infant attentiveness to parent, mutuality) predicted 3-year autism. Attentiveness to parent decreased between 8 and 14 months in EL infants with later autism. This larger study supports previous findings of emerging alterations in PII in this group and extends on this by detecting earlier (8-month) predictive effects of PII for autism outcome and a more marked trajectory of decreased social attentiveness. The findings strengthen the evidence base to support the implementation of early preemptive interventions to support PII in infants with early autism signs., (© 2024 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Alternative fuels are being explored to mitigate the effects of petroleum-based fuels. Pyrolysis oil from waste tires is a promising alternative fuel; however, it contains very high concentrations of benzothiophene (BT) which are beyond the allowable sulfur limits of Taiwan and the Philippines. Mixing-assisted oxidative desulfurization (MAOD) is a method that removes sulfur from fuel oils by utilizing high-shear mixing and oxidants. In this paper, the oxidation of BT in a model fuel was studied to determine optimal process conditions. Crude Fe(VI) prepared from sludge was used as the oxidant. Using the Box-Behnken design under response surface methodology, the significance of the following independent variables was studied: mixing speed (4400-10 800 rpm), phase transfer agent (PTA) amount (100 to 300 mg), Fe(VI) concentration (400-6000 ppm), and mixing temperature (40 to 60 °C). The results from a comprehensive statistical analysis showed the increase of sulfur conversion with high levels of Fe(VI) concentrations and PTA amounts together with low levels of agitation speeds and temperatures. The BT to BT sulfone conversions from experimental runs ranged from 17% to 64%. The optimum sulfur conversion of 88% for the BT model fuel was reached at the maximum levels of Fe(VI) concentration and mixing speed, along with the minimum levels of PTA concentration and temperature. The optimal MAOD variables were applied to a high-sulfur pyrolysis oil sample, which resulted in a sulfur reduction of 55%. The produced fuel oil meets the sulfur requirements of Taiwan and the Philippines for industrial heating oils. Therefore, the findings of the study support the effectiveness of sludge-derived Fe(VI) in the MAOD of BT in the model fuel and pyrolysis oil under mild process conditions., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Crush syndrome often occurs after severe crush injury caused by disasters or accidents, and is associated with high mortality and poor prognosis. Cardiovascular complications, such as cardiac arrest, hypovolemic shock, and hyperkalemia-related cardiac dysfunction, are the primary causes of on-site death in crush syndrome. Prehospital evaluation, together with timely and correct treatment, is of great benefit to crush syndrome patients, which is difficult in most cases due to limited conditions. Based on current data and studies, early fluid resuscitation remains the most important on-site treatment for crush syndrome. Novel solutions and drugs used in fluid resuscitation have been investigated for their effectiveness and benefits. Several drugs have proven effective for the prevention or treatment of cardiovascular complications in crush syndrome, such as hypovolemic shock, hyperkalemia-induced cardiac complications, myocardial ischemia/reperfusion injury, ventricular dysfunction, and coagulation disorder experimentally. Moreover, these drugs are beneficial for other complications of crush syndrome, such as renal dysfunction. In this review, we will summarize the existing on-site treatments for crush syndrome and discuss the potential pharmacological interventions for cardiovascular complications to provide clues for clinical therapy of crush syndrome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Tan, Yang and Yu.)

The importance of supporting parent-child interactions has been noted in the context of prodromal autism, but little consideration has been given to the possible contributing role of parental characteristics, such as psychological distress. This cross-sectional study tested models in which parent-child interaction variables mediated relations between parent characteristics and child autistic behaviour in a sample of families whose infant demonstrated early signs of autism (N = 103). The findings suggest that associations between parent characteristics (psychological distress; aloofness) and child autistic behaviours may be mediated by the child's inattentiveness or negative affect during interactions. These findings have important implications in developing and implementing interventions in infancy which target the synchrony of parent-child interaction with the goal to support children's social communication development., (© 2023. Crown.)

Objective: As a high-efficiency demanding department in a hospital, the outpatient pharmacy has a great need for quality improvement to provide superior medical service for patients. Little is known about the application of 5S management in a hospital pharmacy department. The aim of this study was to evaluate the impacts of 5S management on pharmaceutical service quality and staff capacity in the outpatient-emergency pharmacy., Methods: We carried out a 5S project in the outpatient-emergency pharmacy at a local hospital that involved processes including waste elimination, workplace standardisation, and optimisation of workflow and staff quality, and then evaluated the effects of the project., Results: The equipment and items in the outpatient-emergency pharmacy were sorted. All the drugs were categorised and put in order. The redesigned workspace and standardised workflow during the project improved the accuracy and efficiency of drug dispensing. The satisfaction rate of patients regarding the pharmaceutical service quality in the outpatient-emergency pharmacy was elevated, as well as the satisfaction rate of pharmacists about their work experiences. The optimisation of objective conditions also stimulated a positive working attitude and professional ability promotion of pharmacists in the outpatient-emergency pharmacy., Conclusions: In this study, the 5S management method has proven useful for quality and efficiency improvement in the outpatient-emergency pharmacy, and could be generalised to other departments in a hospital, which provides further evidence of the advantages of the Lean tool in healthcare system management., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study aimed to evaluate the long-term clinical outcomes based on the ligation level of the inferior mesenteric artery (IMA) in patients with rectal cancer., Methods: This was a retrospective analysis of a prospectively collected database that included all patients who underwent elective low anterior resection for rectal cancer between January 2013 and December 2019. The clinical outcomes included oncological outcomes, postoperative complications, and functional outcomes. The oncological outcomes included overall survival (OS) and relapse-free survival (RFS). The functional outcomes, including defecatory and urogenital functions, were analyzed using the Fecal Incontinence Severity Index, International Prostate Symptom Score, and International Index of Erectile Function questionnaires., Results: In total, 545 patients were included in the analysis. Of these, 244 patients underwent high ligation (HL), whereas 301 underwent low ligation (LL). The tumor size was larger in the HL group than in the LL group. The number of harvested lymph nodes (LNs) was higher in the HL group than in the LL group. There were no significant differences in complication rates and recurrence patterns between the groups. There were no significant differences in 5-year RFS and OS between the groups. Cox regression analysis revealed that the ligation level (HL vs. LL) was not a significant risk factor for oncological outcomes. Regarding functional outcomes, the LL group showed a significant recovery in defecatory function 1 year postoperatively compared with the HL group., Conclusion: LL with LNs dissection around the root of the IMA might not affect the oncologic outcomes comparing to HL; however, it has minimal benefit for defecatory function.

Background: Pyroptosis is crucial for controlling various immune cells. However, the role of allergen-induced CD11c + dendritic cell (DC) pyroptosis in allergic rhinitis (AR) remains unclear., Methods: Mice were grouped into the control group, AR group and necrosulfonamide-treated AR group (AR + NSA group). The allergic symptom scores, OVA-sIgE titres, serum IL-1β/IL-18 levels, histopathological characteristics and T-helper cell-related cytokines were evaluated. CD11c/GSDMD-N-positive cells were examined by immunofluorescence analysis. Murine CD11c + bone marrow-derived DCs (BMDCs) were induced in vitro, stimulated with OVA/HDM, treated with necrosulfonamide (NSA), and further cocultured with lymphocytes to assess BMDC function. An adoptive transfer murine model was used to study the role of BMDC pyroptosis in allergic rhinitis., Results: Inhibiting GSDMD-N-mediated pyroptosis markedly protected against Th1/Th2/Th17 imbalance and alleviated inflammatory responses in the AR model. GSDMD-N was mainly coexpressed with CD11c (a DC marker) in AR mice. In vitro, OVA/HDM stimulation increased pyroptotic morphological abnormalities and increased the expression of pyroptosis-related proteins in a dose-dependent manner; moreover, inhibiting pyroptosis significantly decreased pyroptotic morphology and NLRP3, C-Caspase1 and GSDMD-N expression. In addition, OVA-induced BMDC pyroptosis affected CD4 + T-cell differentiation and related cytokine levels, leading to Th1/Th2/Th17 cell imbalance. However, the Th1/Th2/Th17 cell immune imbalance was significantly reversed by NSA. Adoptive transfer of OVA-loaded BMDCs promoted allergic inflammation, while the administration of NSA to OVA-loaded BMDCs significantly reduced AR inflammation., Conclusion: Allergen-induced dendritic cell pyroptosis promotes the development of allergic rhinitis through GSDMD-N-mediated pyroptosis, which provides a clue to allergic disease interventions. Video Abstract., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Attachment-related difficulties frequently present in child and adolescent clinical services. Yet how parents engage with being informed of their child's attachment-related difficulties is little understood. In this qualitative study, ten parents with a birth child with attachment-related difficulties, as informed by a relevant service, and six healthcare professionals, were interviewed. The aim was to explore both perspectives on how parents experienced and engaged with this process, of their understanding of the child's difficulties and the supports they engaged with. Using grounded theory, the parental journey from shame to awareness is described, based around four main themes: failing as a parent , the process of making sense , a call to action, and awareness of attachment and interrelated difficulties . The intensity of shame and defensive processes felt by parents came through strongly in narratives, forming a key barrier to sense-making and action, while specific clinical, personal and support/resource characteristics facilitated progress. The findings highlight how parents can be better supported into a space of attachment-related awareness and understanding, which may in turn facilitate more positive outcomes for the child. The study also raises wide ranging implications relevant to all involved in the investment, planning and delivery of care for this client group.

Background: Various neurologic manifestations have been reported in patients with COVID-19, mostly in retrospective studies of patients admitted to hospital, but there are few data on patients with mild COVID-19. We examined the frequency and persistence of neurologic/neuropsychiatric symptoms in patients with mild COVID-19 in a 1-year prospective cohort study, as well as assessment of use of health care services and patient-reported outcomes., Methods: Participants in the Alberta HOPE COVID-19 trial (hydroxychloroquine v. placebo for 5 d), managed as outpatients, were prospectively assessed 3 months and 1 year after their positive test result. They completed detailed neurologic/neuropsychiatric symptom questionnaires, the telephone version of the Montreal Cognitive Assessment (T-MoCA), the Kessler Psychological Distress Scale (K10) and the EuroQol EQ-5D-3L (measure of quality of life). Close informants completed the Mild Behavioural Impairment Checklist (MBI-C) and the Informant Questionnaire on Cognitive Decline in the Elderly. We also tracked use of health care services and neurologic investigations., Results: The cohort consisted of 198 participants (87 female [43.9%] median age 45 yr, interquartile range 37-54 yr). Of the 179 participants with symptom assessments, 139 (77.6%) reported at least 1 neurologic symptom, the most common being anosmia/dysgeusia (99 [55.3%]), myalgia (76 [42.5%]) and headache (75 [41.9%]). Forty patients (22.3%) reported persistent symptoms at 1 year, including confusion (20 [50.0%]), headache (21 [52.5%]), insomnia (16 [40.0%]) and depression (14 [35.0%]); 27/179 (15.1%) reported no improvement. Body mass index (BMI), a history of asthma and lack of full-time employment were associated with the presence and persistence of neurologic/neuropsychiatric symptoms; female sex was independently associated with both (presence: odds ratio [OR] adjusted for age, race, BMI, history of asthma and neuropsychiatric history 5.04, 95% confidence interval [CI] 1.58 to 16.10). Compared to participants without persistent symptoms, those with persistent symptoms had more hospital admissions and family physician visits, and worse MBI-C scores and less frequent independence for instrumental activities at 1 year (83.8% v. 97.8%, p = 0.005). Patients with any or persistent neurologic symptoms had worse psychologic distress (K10 score ≥ 20: adjusted OR 12.1, 95% CI 1.4 to 97.2) and quality of life (median EQ-5D-3L visual analogue scale rating 75 v. 90, p < 0.001); 42/84 (50.0%) had a T-MoCA score less than 18 at 3 months, as did 36 (42.9%) at 1 year. Participants who reported memory loss were more likely than those who did not report such symptoms to have informant-reported cognitive-behavioural decline (1-yr MBI-C score ≥ 6.5: adjusted OR 15.0, 95% CI 2.42 to 92.60)., Interpretation: Neurologic/neuropsychiatric symptoms were commonly reported in survivors of mild COVID-19, and they persisted in 1 in 5 patients 1 year later. Symptoms were associated with worse participant- and informant-reported outcomes. Trial registration: ClinicalTrials.gov, no. NCT04329611., Competing Interests: Competing interests: Aravind Ganesh reports membership on the editorial boards of Neurology, Stroke and Neurology Clinical Practice; consulting fees and honoraria from Atheneum, MD Analytics, Figure 1, MyMedicalPanel, Creative Research Designs, CTC Communications Corp, Alexion and Biogen; research support from Alberta Innovates, Campus Alberta Neuroscience, the Canadian Cardiovascular Society, the University of Calgary (Hotchkiss Brain Institute), the Sunnybrook Research Institute INOVAIT program and the Canadian Institutes of Health Research (CIHR), outside the submitted work; and stock/stock options from SnapDx and Let’s Get Proof. He has a patent application (US 17/317,771) for a system for prehospital patient monitoring/assessment and delivery of remote ischemic conditioning or other cuff-based therapies. Ryan Rosentreter reports the same patent application (US 17/317,771). Luanne Metz reports grant funding from the MS Society of Canada, outside the submitted work. Eric Smith reports grant funding from the CIHR, Brain Canada and the Weston Brain Institute, outside the submitted work; consulting fees from Bayer, Biogen and Javelin Technologies; royalties from UpToDate; and payment from the American Heart Association for work as associate editor of Stroke. Michael Hill is a director of the Canadian Neurological Sciences Federation and the Canadian Stroke Consortium. He reports consulting fees from BrainsGate; industry grant support to the University of Calgary from NoNO, Biogen, Medtronic and Boehringer-Ingelheim Canada; and public grant support to the University of Calgary from Alberta Innovates, CIHR, the Heart & Stroke Foundation of Canada, and the National Institute of Neurological Disorders and Stroke. He reports a patent to US Patent office (US 62/086,077) issued and licensed. He owns stock in PureWeb. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Competing Interests: None disclosed.

The freshwater crabs Geothelphusa tawu Shy, Ng & Yu, 1994, G. lutao Shy, Ng & Yu, 1994 and G. lanyu Shy, Ng & Yu, 1994 from southern Taiwan and the offshore islets, Lyudao (Green I.) and Lanyu (Orchid I.) are closely related in morphology and genetics, and have been proposed to be the same species. Examination of a series of specimens collected from the distributional ranges of the three species indicated that key characters of the ambulatory legs and the male first gonopod (G1) are too variable to support the identity of three species. Based on the mitochondrial 16S rDNA and cytochrome oxidase subunit I ( COI ) sequences, the phylogenetic analysis did not recover three clades corresponding to the three species, but only a main clade without further clear grouping. The interspecific distances of nucleotides are also too small to support the species delimitation. We conclude that the three species should be treated as a single species. Additionally, unique haplotypes of COI have been found in Lyudao and Lanyu, which are hypothesized as two founder populations that colonized the islets from the Taiwan main island during glacial maxima.

As a lifelong condition, intellectual disability (ID) remains a public health priority. Parents caring for children with ID experience serious challenges to their wellbeing, including depression, anxiety, stress and health-related quality of life. Integrated parenting interventions, which have been well evidenced for depressed mothers, may also effectively support depressed parents with a child with ID in low-resource settings such as Pakistan, and in turn optimise child outcomes. We conducted a mixed-method rater-blind feasibility randomised controlled trial, which assessed the feasibility and acceptability of the Learning Through Play in My Own Way Plus (LTP-IMOW Plus) intervention. Mothers who screened positive for depression (n = 26) with a young child (age 3-6 years) with ID were recruited from two low-resource community settings. Participants in the intervention arm (n = 13) received 12 group sessions of LTP-IMOW Plus and others (n = 13) received routine care. The intervention was feasible and acceptable with 100% retention and 100% session attendance. The intervention improved depression, anxiety, parenting stress and child socialisation score outcomes relative to the routine care arm. The framework utilised to analyse the qualitative interviews with seven participants at pre-intervention identified a range of struggles experienced by the mothers, and at post-intervention, found improved knowledge of child development and practices, improved mother-child relationships, recommendations for the intervention and perceived practical barriers and facilitators. The findings highlight the prospects for a clinical and cost-effective trial of an integrated parenting intervention to manage long-term parental mental health needs and improve child outcomes.

Importance: The growing global prevalence of autism spectrum disorder (ASD) is associated with increasing costs for support services. Ascertaining the effects of a successful preemptive intervention for infants showing early behavioral signs of autism on human services budgets is highly policy relevant., Objective: To estimate the net cost impact of the iBASIS-Video Interaction to Promote Positive Parenting (iBASIS-VIPP) intervention on the Australian government., Design, Setting, and Participants: Infants (aged 12 months) showing early behavioral indicators of autism were recruited through community settings into the multicenter Australian iBASIS-VIPP randomized clinical trial (RCT), a 5- to 6-month preemptive parent-mediated intervention, between June 9, 2016, and March 30, 2018, and were followed up for 18 months to age 3 years. This economic evaluation, including cost analysis (intervention and cost consequences) and cost-effectiveness analyses of iBASIS-VIPP compared with usual care (treatment as usual [TAU]), modeled outcomes observed at age 3 through to 12 years (13th birthday) and was conducted from April 1, 2021, to January 30, 2023. Data analysis was conducted from July 1, 2021, to January 29, 2023., Exposures: iBASIS-VIPP intervention., Main Outcomes and Measures: To project the diagnostic trajectory and associated disability support costs drawing on the Australian National Disability Insurance Scheme (NDIS), the main outcome was the differential treatment cost of iBASIS-VIPP plus TAU vs TAU and disability-related government costs modeled to age 12 years, using a clinical diagnosis of ASD and developmental delay (with autism traits) at 3 years. Costs were calculated in Australian dollars and converted to US dollars. Economic performance was measured through the following: (1) differential net present value (NPV) cost (iBASIS-VIPP less TAU), (2) investment return (dollars saved for each dollar invested, taking a third-party payer perspective), (3) break-even age when treatment cost was offset by downstream cost savings, and (4) cost-effectiveness in terms of the differential treatment cost per differential ASD diagnosis at age 3 years. Alternate values of key parameters were modeled in 1-way and probabilistic sensitivity analysis, the latter identifying the likelihood of an NPV cost savings., Results: Of the 103 infants enrolled in the iBASIS-VIPP RCT, 70 (68.0%) were boys. Follow-up data at age 3 years were available for 89 children who received TAU (44 [49.4%]) or iBASIS-VIPP (45 [50.6%]) and were included in this analysis. The estimated mean differential treatment cost was A $5131 (US $3607) per child  for iBASIS-VIPP less TAU. The best estimate of NPV cost savings was A $10 695 (US $7519) per child (discounted at 3% per annum). For each dollar invested in treatment, a savings of A $3.08 (US $3.08) was estimated; the break-even cost occurred at age 5.3 years (approximately 4 years after intervention delivery). The mean differential treatment cost per lower incident case of ASD was A $37 181 (US $26 138). We estimated that there was an 88.9% chance that iBASIS-VIPP would deliver a cost savings for the NDIS, the dominant third-party payer., Conclusions and Relevance: The results of this study suggest that iBASIS-VIPP represents a likely good-value societal investment for supporting neurodivergent children. The estimated net cost savings were considered conservative, as they covered only third-party payer costs incurred by the NDIS and outcomes were modeled to just age 12 years. These findings further suggest that preemptive interventions may be a feasible, effective, and efficient new clinical pathway for ASD, reducing disability and the costs of support services. Long-term follow-up of children receiving preemptive intervention is needed to confirm the modeled results.

Background: Over the last 20 years, compassion focused therapy (CFT) has gained popularity as an emerging 'third wave' intervention. Although previous reviews indicated its potential benefits, a systematic review and meta-analysis of CFT in those with mental health difficulties has yet to be conducted., Methods: A systematic search of five databases was undertaken, focusing on randomised controlled trials and randomised pilot/feasibility studies of CFT only. No language restrictions were implemented. A narrative synthesis was conducted. Random effects meta-analyses were measured on levels of self-compassion, self-criticism/self-reassurance, fears of compassion and clinical symptomology., Results: Fifteen studies from 2013 to 2022 were included. Findings suggested that CFT was effective in improving compassion-based outcomes and clinical symptomology from baseline to post-intervention and compared to waitlist control. A range of small to large effect sizes were reported for improvements in self-compassion (0.19-0.90), self-criticism (0.15-0.72), self-reassurance (0.43-0.81), fear of self-compassion (0.18), depression (0.24-0.25) and eating disorders (0.18-0.79). Meta-analyses favoured CFT in improving levels of self-compassion and self-reassurance than control groups., Limitations: The methodological quality of many of the included studies (7/15) was rated as 'unclear' due to a lack of information. There was a distinct gender gap, with 74.88% identifying as female participants., Conclusions: This review was the first to examine the effectiveness of CFT in clinical populations. The results indicate that CFT has promising clinical implications, suggesting that the intervention increases compassion-based outcomes and reduces clinical symptomology in those with mental health difficulties. However, future research is required into the long-term effects of CFT., Competing Interests: Conflict of interest The authors declare that they do not have any conflict of interest. This review was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Natural Language Sampling (NLS) offers clear potential for communication and language assessment, where other data might be difficult to interpret. We leveraged existing primary data for 18-month-olds showing early signs of autism, to examine the reliability and concurrent construct validity of NLS-derived measures coded from video-of child language, parent linguistic input, and dyadic balance of communicative interaction-against standardised assessment scores. Using Systematic Analysis of Language Transcripts (SALT) software and coding conventions, masked coders achieved good-to-excellent inter-rater agreement across all measures. Associations across concurrent measures of analogous constructs suggested strong validity of NLS applied to 6-min video clips. NLS offers benefits of feasibility and adaptability for validly quantifying emerging skills, and potential for standardisation for clinical use and rigorous research design., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

While theory supports bidirectional effects between caregiver sensitivity and language use, and infant language acquisition-both caregiver-to-infant and also infant-to-caregiver effects-empirical research has chiefly explored the former unidirectional path. In the context of infants showing early signs of autism, we investigated prospective bidirectional associations with 6-min free-play interaction samples collected for 103 caregivers and their infants (mean age 12-months; and followed up 6-months later). We anticipated that measures of caregiver sensitivity/language input and infant language would show within-domain temporal stability/continuity, but also that there would be predictive associations from earlier caregiver input to subsequent child language, and vice versa. Caregiver sensitive responsiveness (from the Manchester Assessment of Caregiver-Infant interaction [MACI]) predicted subsequent infant word tokens (i.e., amount of language, coded following the Systematic Analysis of Language Transcripts [SALT]). Further, earlier infant Mean Length of Utterance (MLU; reflecting language complexity, also derived from SALT coding) predicted later caregiver MLU, even when controlling for variability in infant ages and clear within-domain temporal stability/continuity in key measures (i.e., caregiver sensitive responsiveness and infant word tokens; and infant and caregiver MLU). These data add empirical support to theorization on how caregiver input can be both supportive of, and potentially influenced by, infant capacities, when infants have social-communication differences and/or communication/language delays suggestive of possible emerging autism., (© 2022 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Migrants living in Europe constitute over half of the world's international migrants and are at higher risk of poor mental health than non-migrants, yet also face more barriers in accessing and engaging with services. Furthermore, the quality of care received is shaped by the experiences and attitudes of health professionals. The aim of this review was to identify professionals' attitudes towards migrants receiving mental healthcare and their perceptions of barriers and facilitators to service provision. Four electronic databases were searched, and 23 studies met the inclusion criteria. Using thematic synthesis, we identified three themes: 1) the management of multifaceted and complex challenges associated with the migrant status; 2) professionals' emotional responses to working with migrants; and 3) delivering care in the context of cultural difference. Professionals employed multiple strategies to overcome challenges in providing care yet attitudes towards this patient group were polarized. Professionals described mental health issues as being inseparable from material and social disadvantage, highlighting a need for effective collaboration between health services and voluntary organizations, and partnerships with migrant communities. Specialist supervision, reflective practice, increased training for professionals, and the adoption of a person-centered approach are also needed to overcome the current challenges in meeting migrants' needs. The challenges experienced by health professionals in attempting to meet migrant needs reflect frustrations in being part of a system with insufficient resources and without universal access to care that effectively stigmatizes the migrant status.

Identifying cold-related genes can provide insights into the cold adaptation mechanism of weeping forsythia. In this study, we compared the changes in gene expressions and physiological and biochemical indices under short-term cold stimulation with the changes in gene sequences under a long-term heterogeneous environment to investigate the cold adaptation mechanism in weeping forsythia. The data of adaptive gene sequence changes, e.g., single nucleotide polymorphisms, were obtained from previous landscape genomics studies. The physiological and biochemical indicators and transcriptome results showed that weeping forsythia initiated a series of programs, including increasing cell osmotic pressures, scavenging ROS, activating the defense mechanism that crosses with pathogen infection, and upregulating CBF/DREB1 transcription factor 1, to cope with short-term cold stress. A reanalysis of landscape genomic data suggested that weeping forsythia responded to long-term heterogeneous cold stress by the differentiation of genes related to synthesis of aromatic substances and adenosine triphosphate. Our results supported the hypothesis that the adaptation mechanisms of species to short-term environmental stimulation and long-term stress in heterogeneous environments are different. The differences in cold tolerance among populations are not necessarily obtained by changing cold-responsive gene sequences. This study provides new insights into the cold adaptation mechanisms of plants., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: Central and Eastern European (CEE) migrants are a large minority group in the UK who are vulnerable to experiencing mental health problems. However, due to their shared 'whiteness' with the majority population, health service disparities may be overlooked. This is the first study exploring CEE-born people's experiences of mental health services post-Brexit., Method: Thirteen CEE migrants who had received mental health services in the UK were interviewed and data was thematically analysed., Results: Barriers and facilitators to engagement reflected: 1) attitudes towards help-seeking; 2) cultural in/visibility; and 3) professional-service user communication. Some barriers were unique to the CEE community and not shared by other minority groups, such as the 'invisibility' of ethnic identity and this framed the way participants navigated interactions with services., Conclusions: Cultural differences and mental health stigma were reported to influence understanding of mental health, attitudes to help-seeking, and experiences of services. Flexible ethnic identity and majority group "passing" could conceal inequalities in healthcare., Practice Implications: The need for culturally informed approaches, professional upskilling, strengthened inter-agency working, and collaboration with CEE communities. The need to build on pre-existing strengths, for self-directed and self-care activities, for appropriate pacing and confidentiality discussions, and the use of web-based resources., Competing Interests: Declaration of Competing Interests The authors report no competing interests. All authors have contributed significantly, and all authors agree with the content of the manuscript., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The corresponding mRNA vaccines Comirnaty (BNT162b2) and Spikevax (mRNA-1273) have been authorized for emergency use since the COVID-19 outbreak. Most clinical researches have also discovered that the mRNA vaccine is a revolutionary strategy for preventing and treating numerous diseases, including cancers. Unlike viral vectors or DNA vaccines, mRNA vaccines cause the body to directly produce proteins following injection. Delivery vectors and mRNAs that encode tumor antigens or immunomodulatory molecules work together to trigger an anti-tumor response. Before mRNA vaccines may be employed in clinical trials, a number of challenges need to be resolved. These include establishing effective and safe delivery systems, generating successful mRNA vaccines against diverse types of cancers, and proposing improved combination therapy. Therefore, we need to improve vaccine-specific recognition and develop mRNA delivery mechanisms. This review summarizes the complete mRNA vaccines' elemental composition and discusses recent research progress and future direction for mRNA tumor vaccines., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Longitudinally extensive spinal cord lesions are challenging diagnostic entities as they are uncommon, but various etiologies can cause them., Case Report: We report a case of a 55-year-old man with a past medical history of hypertension. He is an ex-smoker. He presented with chest pain, followed by right lower limb weakness, preceded by 2 weeks of constipation and voiding dysfunction. The examination revealed right lower limb mild flaccid paresis, absent reflexes, reduced anal tone, and urinary retention. His symptoms deteriorated over 24 h, and he developed severe flaccid paraparesis with impaired pinprick sensation below the T4 level. MRI spine showed an abnormal, non-enhancing signal in the anterior aspect of the spinal cord extending from the T4 level to the conus without associated edema. He was commenced on intravenous steroids and had significant improvement after one dose. The imaging was felt to be consistent with spinal cord infarction, and aspirin was started. The cerebrospinal fluid analysis showed elevated protein (0.8 mg/ml). Investigations for stroke and autoimmune pathologies were negative. The Lyme immunoblot confirmed intrathecal production of IgG to Borrelia antigens. The patient was started on ceftriaxone. The paraneoplastic screen identified amphiphysin antibodies. CT-TAP and PET-CT did not identify occult malignancy. The patient had a significant improvement over 2 months, strength was almost fully recovered, and autonomic functions returned to normal., Conclusion: We describe an unusual steroid-responsive, longitudinally extensive spinal cord lesion with radiological features of spinal cord infarct and a simultaneous finding of intrathecal Lyme antibodies and serum amphiphysin antibodies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kalaszi, Donlon, Ahmad, Mohamed and Boers.)

Internalising problems are common within Autism Spectrum Disorder (ASD); early intervention to support those with emerging signs may be warranted. One promising signal lies in how individual differences in temperament are shaped by parenting. Our longitudinal study of infants with and without an older sibling with ASD investigated how parenting associates with infant behavioural inhibition (8-14 months) and later effortful control (24 months) in relation to 3-year internalising symptoms. Mediation analyses suggest nondirective parenting (8 months) was related to fewer internalising problems through an increase in effortful control. Parenting did not moderate the stable predictive relation of behavioural inhibition on later internalising. We discuss the potential for parenting to strengthen protective factors against internalising in infants from an ASD-enriched cohort., (© 2021. The Author(s).)

Background: Sepsis is an important cause of mortality and morbidity among critically ill patients with underlying malignancy., Methods: Patients with sepsis admitted to the intensive care unit (ICU) of the Pamela Youde Nethersole Eastern Hospital from January 1, 2010 to April 30, 2019 were recruited. Demographics, laboratory parameter, and outcome were analyzed. Those with underlying malignancy were matched with those without malignancy based on their severity of organ failure (defined by the sequential organ failure assessment [SOFA] score) and septic source., Results: Two hundred sixty-three patients with underlying active malignancy were matched with 259 patients without malignancy. Those with malignancy had higher APACHE IV score (89 vs. 83), lower albumin (22.1 vs. 24.4), neutrophil count (6.0 vs. 9.3), hemoglobin (8.0 vs. 9.8), platelet count (113 vs. 133), less use of mechanical ventilation (35.7% vs. 45.9%), renal replacement therapy (22.1% vs. 28.2%) and vasopressor (66.2% vs. 74.9%), higher 30-day (34.2% vs. 24.3%) ICU (22.4% vs. 18.9%), and 1-year (62.4% vs. 36.7%) mortality compared with those without malignancy. A higher APACHE IV score and pulmonary sepsis were predictors of 30-day mortality by Cox regression analysis., Conclusion: Disease severity and pulmonary sepsis, but not underlying malignancy, predicted short-term mortality among critically ill septic patients., (© 2021 John Wiley & Sons Australia, Ltd.)

Neurosteroids have been associated with neurodegenerative diseases because they are involved in the modulation of neurotransmitter, neurotropic and neuroprotective actions. Emerging evidence suggests that the enzymes responsible for the synthesis of neurosteroids change during the progression of Alzheimer's disease (AD). The present study aimed to assess the changes in phase I and II enzymes involved in the metabolism of neurosteroids of the progestogen, androgenic and estrogenic steroidogenic pathways and the possibility that the neurosteroids are actively converted into the most abundant metabolites (i.e. glucuronides and sulphates). The gene expression for the phase I and II neurosteroid biosynthetic enzymes were studied in the hippocampus of streptozotocin AD rat model. Male Sprague-Dawley rats were randomly divided into control, sham (saline injected into the hippocampus) and 3 and 12 weeks post-STZ administration (STZ-G3w and STZ-G12w, respectively) groups. Behavioral assessments showed memory impairment in both STZ-injected groups, whereas the formation of amyloid-beta was more pronounced in the STZ-12w group. Gene expression of the hippocampus revealed that glucuronidation and sulphation enzymes transcript of the phase I metabolites were upregulated at the late stage of the disease progression (Hsd17b10, Hsd3b1, Akr1c3 and Cyp19a1) except for Sts. The phase II Sult and Ugt enzymes were mostly upregulated in the STZ-G12w rats (Sult1a1, Sult1e1, Ugt1a1, Ugt1a7c, Ugt1a6, Ugt2b35 and Ugt2b17) and normally expressed in the STZ-G3w group (Sult2a2, Sult2a6, Sult2b1, Ugt2b7, Sult4a1 and Ugt1a7c). In conclusion, changes occur in the phase I and II enzymes transcript of the progestogen, androgenic and estrogenic steroidogenic pathways during the progression of AD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To examine the trajectories of cognitive, motor and behavioural development in infants with NF1 compared to infants without a family history of neurodevelopmental difficulties., Study Design: Infants with NF1 and low-risk controls were recruited from 5 months of age and followed longitudinally. Data from standardised tests was gathered at 5, 10 and 14 months and developmental trajectories of motor, language, behaviour, sleep, social development and parent-infant interaction were examined. Linear mixed modelling was used to estimate group differences in cognitive and behavioural measures over time., Results: No group differences were observed on Mullen Scale of Early Learning, overall adaptive functioning, temperament or behavioural measures. There were no group differences observed on measures of social communication or parent-infant interaction. Over the course of development, the NF1 group slept less and took more time to settle to sleep as compared to the control group. Maternal education was significantly associated with cognitive and behavioural developmental outcomes in both groups., Conclusion: Cognitive, social and behavioural impairments are a cause of significant functional morbidity in children with NF1. This report is the first study to investigate the trajectories of cognitive, motor and behavioural development in infancy in NF1. Our results demonstrate that overall cognitive and behavioural developmental trajectories of the NF1 group in the infancy period are similar to controls. Given previous reports of delayed development in the NF1 cohort by 40 months, early clinical interventions strategies to promote sleep hygiene may be beneficial to optimise developmental outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garg, Wan, Begum-Ali, Kolesnik-Taylor, Green, Johnson and Jones.)

Oxygen is essential for most life forms. Insufficient oxygen supply can disrupt homeostasis and compromise survival, and hypoxia-induced cardiovascular failure is fatal in many animals, including humans. However, certain species have adapted and evolved to cope with hypoxic environments and are therefore good models for studying the regulatory mechanisms underlying responses to hypoxia. Here, we explored the physiological and molecular responses of the cardiovascular system in two closely related hypoxia-adapted species with different life histories, namely, Qinghai voles ( Neodon fuscus ) and Brandt's voles ( Lasiopodomys brandtii ), under hypoxic (10% O 2 for 48 h) and normoxic (20.9% O 2 for 48 h) exposure. Kunming mice ( Mus musculus ) were used for comparison. Qinghai voles live in plateau areas under hypoxic conditions, whereas Brandt's voles only experience periodic hypoxia. Histological and hematological analyses indicated a strong tolerance to hypoxia in both species, but significant cardiac tissue damage and increased blood circulation resistance in mice exposed to hypoxia. Comparative transcriptome analysis revealed enhanced oxygen transport efficiency as a coping mechanism against hypoxia in both N. fuscus and L. brandtii , but with some differences. Specifically, N. fuscus showed up-regulated expression of genes related to accelerated cardiac contraction and angiogenesis, whereas L. brandtii showed significant up-regulation of erythropoiesis-related genes. Synchronized up-regulation of hemoglobin synthesis-related genes was observed in both species. In addition, differences in cardiometabolic strategies against hypoxia were observed in the rodents. Notably, M. musculus relied on adenosine triphosphate (ATP) generation via fatty acid oxidation, whereas N. fuscus shifted energy production to glucose oxidation under hypoxic conditions and L. brandtii employed a conservative strategy involving down-regulation of fatty acid and glucose oxidation and a bradycardia phenotype. In conclusion, the cardiovascular systems of N. fuscus and L. brandtii have evolved different adaptation strategies to enhance oxygen transport capacity and conserve energy under hypoxia. Our findings suggest that the coping mechanisms underlying hypoxia tolerance in these closely related species are context dependent.

A previously healthy 27-year-old man was brought to hospital after been found late at night confused, agitated and talking incoherently. He represented 12 days later with focal seizures, progressing to anarthria and encephalopathy. MR scan of brain showed diffuse cerebral oedema and his plasma ammonia was >2000 µmol/L (12-55 µmol/L). He developed refractory status epilepticus and subsequently died. Genetic analysis identified an ornithine transcarbamylase (OTC) gene mutation on the X chromosome. We discuss this atypical presentation of OTC deficiency as a rare but treatable cause of hyperammonaemic encephalopathy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

In this study, fixed-bed adsorption of Pb(II) from an aqueous solution using chitosan-coated bentonite (CCB) was investigated. Characterization of CCB was performed using Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The effects of varying bed height (1.3 to 4.3 cm), flow rate (0.20 to 0.60 mL/min), and initial concentration (500 to 1500 mg/L) on the length of mass transfer zone ( Z m ) and adsorption capacity at breakthrough ( q b ) and exhaustion ( q e ) were examined. Low flow rate and high bed height were determined to cause a longer time to reach breakthrough and exhaustion. Meanwhile, the fixed-bed system was observed to quickly attain breakthrough and exhaustion under high initial concentrations. Kinetic column models such as the Thomas, Yoon-Nelson, and Clark models were used to predict the breakthrough curves. High R 2 values (0.9758 ≤ R 2 ≤ 0.8087) were attained for the Thomas model, which indicates that there is good agreement between experimental data and linear plots generated by the Thomas model. Moreover, the Thomas model is best in describing the breakthrough curves of Pb(II) removal under a fixed-bed system.

The process of protein ubiquitination and deubiquitination plays an important role in maintaining protein stability and regulating signal pathways, and protein homeostasis perturbations may induce a variety of diseases. The deubiquitination process removes ubiquitin molecules from the protein, which requires the participation of deubiquitinating enzymes (DUBs). Ubiquitin-specific protease 15 (USP15) is a DUB that participates in many biological cell processes and regulates tumorigenesis. A dislocation catalytic triplet was observed in the USP15 structure, a conformation not observed in other USPs, except USP7, which makes USP15 appear to be unique. USP15 has been reported to be involved in the regulation of various cancers and diseases, and the reported substrate functions of USP15 are conflicting, suggesting that USP15 may act as both an oncogene and a tumor suppressor in different contexts. The importance and complexity of USP15 in the pathological processes remains unclear. Therefore, we reviewed the diverse biological functions of USP15 in cancers and other diseases, suggesting the potential of USP15 as an attractive therapeutic target.

Context: Astaxanthin (Ast), a compound used widely as a dietary supplement, has high antioxidant properties but poor oral bioavailability. To benefit from its nutritional values in cognitive function, Ast was formulated into a nanoemulsion which may improve its penetration through the blood-brain barrier (BBB)., Aim: The present study aims to quantitate the Ast nanoemulsion in different regions of the brain tissue using the high-performance liquid chromatography method., Materials and Methods: Sprague-Dawley rats were fed with Ast nanoemulsion formulation daily (40, 80, and 160 mg/kg body weight, bw) for 28 days before brain tissues were harvested, extracted, and quantified. A simple, sensitive, and reliable method using high-performance liquid chromatography with an ultraviolent detector was developed and validated to quantify Ast in the brain., Statistical Analysis: Data were analyzed using the ToolPak Data Analysis in Excel for t -test and analysis of variance single factor with Tukey post hoc analysis., Results: The calibration curve demonstrated a linear regression with an r 2 of 0.9998 and absolute recovery ranging from 97.8% to 109.6%. The hippocampus of the 160 mg/kg bw treatment group showed a significantly higher concentration of Ast (77.9 ± 17.3 μg/g) compared to the cortex (22.3 ± 4.2 μg/g) and cerebellum (33.1 ± 5.4 μg/g). Ast was detected in the cerebellum of the 80 mg/kg bw (29.4 ± 7.8 μg/g) treatment group with the amount not being significantly different to the 160 mg/kg bw (33.1 ± 5.4 μg/g) treatment group., Conclusions: It was evident that the Ast nanoemulsion formulated was able to cross the BBB and may provide protective benefits., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Pharmacy and Bioallied Sciences.)

Child temperament and caregiver psychological distress have been independently associated with social-emotional difficulties among individuals with autism. However, the interrelationship among these risk factors has rarely been investigated. We explored the reciprocal interplay between child temperament (surgency, negative affectivity, and self-regulation) and caregiver psychological distress in the development of child internalizing and externalizing symptoms, in a cohort of 103 infants showing early autism traits. Caregivers completed questionnaires when children were aged around 12-months (Time 1 [T1]), 18-months (Time 2 [T2]), and 24-months (Time 3 [T3]). Cross-lagged path models revealed a significant pathway from T1 caregiver psychological distress through lower T2 child self-regulation to subsequently greater T3 child internalizing symptoms. No such caregiver-driven pathway was evident through T2 child negative affectivity or in the prediction of T3 child externalizing symptoms. Further, no support was found for temperament-driven pathways through caregiver psychological distress to child social-emotional difficulties. Child surgency was mostly unrelated to caregiver psychological distress and social-emotional difficulties. These findings implicate the need to support the mental health of caregivers with an infant with autism traits in order to enhance the emotion regulation and social-emotional development of their infants., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hypertension is one of the major causes of public health problems. Multiple factors affecting gastrointestinal tract function are involved in hypertension. Emerging studies have manifested that gut intervention may play significant roles in regulating blood pressure but the underlying mechanisms are complex and not fully clear. Here, we report a case of 66 years old male who had a long history of hypertension and received Miles surgery for rectal carcinoma. The blood pressure of this patient was returned to normal levels after the operation. The possible reasons could be the modulation of sympathetic tone and the gut microbiota-brain axis. This report provides evidence about the relevance between hypertension and gut intervention particularly in the colorectal sites and gives hints for investigating the possible mechanisms of hypertension and the novel strategy for blood pressure control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Fan and Yu.)

Importance: Intervention for individuals with autism spectrum disorder (ASD) typically commences after diagnosis. No trial of an intervention administered to infants before diagnosis has shown an effect on diagnostic outcomes to date., Objective: To determine the efficacy of a preemptive intervention for ASD beginning during the prodromal period., Design, Setting, and Participants: This 2-site, single rater-blinded randomized clinical trial of a preemptive intervention vs usual care was conducted at 2 Australian research centers (Perth, Melbourne). Community sampling was used to recruit 104 infants aged 9 to 14 months showing early behaviors associated with later ASD, as measured by the Social Attention and Communication Surveillance-Revised. Recruitment occurred from June 9, 2016, to March 30, 2018. Final follow-up data were collected on April 15, 2020., Interventions: Infants were randomized on a 1:1 ratio to receive either a preemptive intervention plus usual care or usual care only over a 5-month period. The preemptive intervention group received a 10-session social communication intervention, iBASIS-Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care comprised services delivered by community clinicians., Main Outcomes and Measures: Infants were assessed at baseline (approximate age, 12 months), treatment end point (approximate age, 18 months), age 2 years, and age 3 years. Primary outcome was the combined blinded measure of ASD behavior severity (the Autism Observation Scale for Infants and the Autism Diagnostic Observation Schedule, second edition) across the 4 assessment points. Secondary outcomes were an independent blinded clinical ASD diagnosis at age 3 years and measures of child development. Analyses were preregistered and comprised 1-tailed tests with an α level of .05., Results: Of 171 infants assessed for eligibility, 104 were randomized; 50 infants (mean [SD] chronological age, 12.40 [1.93] months; 38 boys [76.0%]) received the iBASIS-VIPP preemptive intervention plus usual care (1 infant was excluded after randomization), and 53 infants (mean [SD] age, 12.38 [2.02] months; 32 boys [60.4%]) received usual care only. A total of 89 participants (45 in the iBASIS-VIPP group and 44 in the usual care group) were reassessed at age 3 years. The iBASIS-VIPP intervention led to a reduction in ASD symptom severity (area between curves, -5.53; 95% CI, -∞ to -0.28; P = .04). Reduced odds of ASD classification at age 3 years was found in the iBASIS-VIPP group (3 of 45 participants [6.7%]) vs the usual care group (9 of 44 participants [20.5%]; odds ratio, 0.18; 95% CI, 0-0.68; P = .02). Number needed to treat to reduce ASD classification was 7.2 participants. Improvements in caregiver responsiveness and language outcomes were also observed in the iBASIS-VIPP group., Conclusions and Relevance: Receipt of a preemptive intervention for ASD from age 9 months among a sample of infants showing early signs of ASD led to reduced ASD symptom severity across early childhood and reduced the odds of an ASD diagnosis at age 3 years., Trial Registration: http://anzctr.org.au identifier: ACTRN12616000819426.

Background: Previous studies have reported that olfactory identification deficits may be the earliest clinical features of Alzheimer's disease (AD). However, the association between odor identification and hippocampal atrophy remains unclear. Objective: This meta-analysis quantified the correlation between odor identification test scores and hippocampal volume in AD. Method: A search of the PUBMED, EMBASE, and WEB OF SCIENCE databases was conducted from January 2003 to June 2020 on studies with reported correlation coefficients between olfactory identification score and hippocampal volume in patients with amnestic AD or mild cognitive impairment (MCI). The quality of the studies was assessed using the Newcastle-Ottawa quality assessment scale (NOS). Pooled r- values were combined and computed in R studio. Results: Seven of 627 original studies on AD/MCI using an olfactory identification test ( n = 902) were included. A positive correlation was found between hippocampal volume and olfactory test scores ( r = 0.3392, 95% CI: 0.2335-0.4370). Moderator analysis showed that AD and MCI patients were more profoundly correlated than normal controls (AD: r = 0.3959, 95% CI: 0.2605-0.5160; MCI: r = 0.3691, 95% CI: 0.1841-0.5288; NC: r = 0.1305, 95% CI: -0.0447-0.2980). Age difference and patient type were the main sources of heterogeneity in this analysis. Conclusion: The correlation appears to be more predominant in the cognitive disorder group (including MCI and AD) than in the non-cognitive disorder group. Age is an independent factor that affects the severity of the correlation during disease progression. The mildness of the correlation suggests that olfactory tests may be more accurate when combined with other non-invasive examinations for early detection. Systematic Review Registration: https://inplasy.com/, identifier INPLASY202140088., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Su, Ni, Cao, Wang, Shi and Tian.)

Cardio-cerebrovascular diseases, as a major cause of health loss all over the world, contribute to an important part of the global burden of disease. A large number of traditional Chinese medicines have been proved effective both clinically and in pharmacological investigations, with the acceleration of the modernization of Chinese medicine. Sinomenine is the main active constituent of sinomenium acutum and has been generally used in therapies of rheumatoid arthritis and neuralgia. Varieties of pharmacological effects of sinomenine in cardio-cerebrovascular system have been discovered recently, suggesting an inspiring application prospect of sinomenine in cardio-cerebrovascular diseases. Sinomenine may retard the progression of atherosclerosis by attenuating endothelial inflammation, regulating immune cells function, and inhibiting the proliferation of vascular smooth muscle cells. Sinomenine also alleviates chronic cardiac allograft rejection relying on its anti-inflammatory and anti-hyperplastic activities and suppresses autoimmune myocarditis by immunosuppression. Prevention of myocardial or cerebral ischemia-reperfusion injury by sinomenine is associated with its modulation of cardiomyocyte death, inflammation, calcium overload, and oxidative stress. The regulatory effects on vasodilation and electrophysiology make sinomenine a promising drug to treat hypertension and arrhythmia. Here, in this review, we will illustrate the pharmacological activities of sinomenine in cardio-cerebrovascular system and elaborate the underlying mechanisms, as well as give an overview of the potential therapeutic roles of sinomenine in cardio-cerebrovascular diseases, trying to provide clues and bases for its clinical usage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Wang, Shi and Yu.)

Pterocarya stenoptera is a tree species that occurs along rivers and has high tolerance to waterlogging. Identification of waterlogging response genes in the aboveground part of P. stenoptera will increase understanding of tolerance mechanisms under root waterlogging conditions. In this study, we employed four physiological indicators and comparative transcriptome sequencing to investigate the waterlogging tolerance mechanism in P. stenoptera. The physiological results showed that the aboveground part of P. stenoptera was not obviously affected by waterlogging. P. stenoptera enhanced waterlogging tolerance by increasing the synthesis of alpha-Linolenic acids and flavonoids and activating the jasmonic acid, ethylene, and auxin signaling pathways. Our results confirmed our hypothesis that P. stenoptera, a species that is widely distributed along rivers, has evolved a range of mechanisms in response to waterlogging. Our research will provide new insights for understanding the tolerance mechanism of species to waterlogging., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Colorectal cancer is a common malignancy with the third highest incidence and second highest mortality rate among all cancers in the world. Chemotherapy resistance in colorectal cancer is an essential factor leading to the high mortality rate. The ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) confers multidrug resistance (MDR) to a range of chemotherapeutic agents by decreasing their intracellular content. The development of novel ABCG2 inhibitors has emerged as a tractable strategy to circumvent drug resistance. In this study, an ABCG2-knockout colorectal cancer cell line was established to assist inhibitor screening. Additionally, we found that ataxia-telangiectasia mutated (ATM) kinase inhibitor AZ32 could sensitize ABCG2-overexpressing colorectal cancer cells to ABCG2 substrate chemotherapeutic drugs mitoxantrone and doxorubicin by retaining them inside cells. Western blot assay showed that AZ32 did not alter the expression of ABCG2. Moreover, molecule docking analysis predicted that AZ32 stably located in the transmembrane domain of ABCG2. In conclusion, our result demonstrated that AZ32 could potently reverse ABCG2-mediated MDR in colorectal cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Li, Chen, Shi, Xing, He, Wang, Liu, Zhang, Yu, Mo, Chen, Chen and Shi.)

As a consequence of hybridization, polyploidization, and apomixis, the genus Cotoneaster (Rosaceae) represents one of the most complicated and controversial lineages in Rosaceae, with ca. 370 species which have been classified into two subgenera and several sections, and is notorious for its taxonomic difficulty. The infrageneric relationships and taxonomy of Cotoneaster have remained poorly understood. Previous studies have focused mainly on natural hybridization involving only several species, and phylogeny based on very limited markers. In the present study, the sequences of complete chloroplast genomes and 204 low-copy nuclear genes of 72 accessions, representing 69 species as ingroups, were used to conduct the most comprehensive phylogenetic analysis so far for Cotoneaster. Based on the sequences of complete chloroplast genomes and many nuclear genes, our analyses yield two robust phylogenetic trees respectively. Chloroplast genome and nuclear data confidently resolved relationships of this genus into two major clades which largely supported current classification based on morphological evidence. However, conflicts between the chloroplast genome and low-copy nuclear phylogenies were observed in both the species level and clade level. Cyto-nuclear discordance in the phylogeny could be caused by frequent hybridization events and incomplete sorting lineage (ILS). In addition, our divergence-time analysis revealed an evolutionary radiation of the genus from late Miocene to date., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Lysyl oxidase-like 3 (LOXL3) is an extracellular enzyme involved in the synthesis of collagen and elastin, and it has been reported to promote melanoma cell proliferation and invasion in vitro. However, the expression level of LOXL3 at different stages of melanocytic lesions and the role of LOXL3 in melanoma pathogenesis remain unknown. Immunohistochemical staining of LOXL3 in a tissue microarray of 373 biopsies at different melanocytic stages was conducted. The correlation between LOXL3 expression and patient survival was examined using Kaplan-Meier survival analysis. Univariate and multivariate Cox regression analyses were conducted to study the hazard ratios. The tissue microarray study revealed that stronger expression of LOXL3 protein was found at more advanced melanocytic stages (P < 0.0001; χ2 test). Increased LOXL3 expression was associated with enhanced tumor thickness and mitosis. Survival analysis showed significantly worsened prognosis in primary melanoma patients when the LOXL3 expression level was higher (P = 0.043; log-rank test). Multivariate Cox regression analysis further showed that LOXL3 expression is a prognostic factor for primary melanoma patient survival (P = 0.04). LOXL3 expression is positively correlated with tumor progression and invasion, and its overexpression is associated with worse prognosis of primary melanoma patients. LOXL3 can serve as a prognostic marker to help identify primary melanoma patients at higher risks of death., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Human infants are "wired" to respond to social information, an important capacity for survival. The ability to discriminate vocal emotion in others is likely to play a key role in successful social interactions with caregivers, which facilitate the rapid social-communicative development that infants typically undergo in the latter half of their first year. Infants have voice-sensitive brain regions that have been shown previously to be responsive to emotional prosody by 7 months. This study aimed to investigate the developmental trajectory of vocal emotion processing in temporal regions using functional near-infrared spectroscopy (fNIRS) to measure brain sensitivity to angry, happy, and neutral vocalizations in the same infant at 6, 9, and 12 months. We found significant and increasing temporal cortical activation in response to vocal emotional stimuli over the three time points, suggesting consistent enhanced responses for happy compared to angry vocalizations, and vocal anger sensitivity is developing incrementally. The findings suggest that the neural processing of angry and happy prosody may follow distinct developmental pathways and is gradually "tuned" to become specialized between 6 and 12 months. This first longitudinal study of vocal emotion brain processing between 6 and 12 months highlights the need for more research to understand what drives typical and atypical social cognitive development across infancy and for follow-up into the second year.

Objectives: This study aimed to evaluate the effect of a closed-loop computerised physician order entry (CPOE) system on prescribing in a general paediatric unit in Hong Kong. We studied the effect of the CPOE system on medication prescribing error and the characteristics of these errors before and after the implementation of the system., Methods: This was a single-site, prospective, observational study at a public hospital's general paediatric unit in Hong Kong, conducted during the pre- and post-implementation of the system from March to April 2019 and 2020, respectively. Collected data included the number of medication orders processed, the number of prescribing errors identified, and the characteristics of errors, such as the severity, children's age group, drug formulation, and drug class., Key Findings: The prescribing error rate was significantly reduced from 6.7% to 3.9% after CPOE implementation. The causes of prescribing errors were found to be significantly different, as the implementation eradicated handwriting-related errors and reduced dosage selection-related errors. However, we found that CPOE increased other causes of error, such as missing entry of patient information that might affect the dispensing process, thus delaying patients in receiving their medications on time., Conclusion: The CPOE system significantly reduced prescribing errors and altered some of the characteristics of these errors. Poor system design or inadequate user training could result in the creation of new causes of error., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Maternal mental disorder and a negative family emotional climate are a great source of stress for many children, yet their role in the childhood development or expression of asthma and allergies remains poorly understood, particularly beyond the first 1-2 years of life. The current study tested whether childhood allergy onset and symptomatology would be predicted by (1) perinatal and any time exposure to maternal depression or anxiety and (2) current family emotional strain (whole family, mother-child). UK mothers of children aged 2-12 years (N = 328) living with them completed an online survey of measures. Children exposed to maternal depression were almost twice as likely to be diagnosed and almost five times as likely to screen positive for an allergic disorder. Perinatal depression was linked to childhood allergies, but more moderately. Any anxiety exposure, and not specific to the perinatal period, predicted allergy status. Family emotional strain contributed independently to variance in concurrent child allergic symptomatology. All results were independent of potential confounders and current mental distress. The findings highlight the importance of maternal mental health and family function in the child's neuro-immune development, and that these factors need to be addressed in the treatment of childhood allergic disorders.

There has been little research on whether and how screen media usage affects social-emotional (SE) function prior to two years of age, even though early SE development is understood to be nurtured through interpersonal experience, mainly withthe primary caregiver. This study sought to characterise infant screen media usage and understand how it may link with concurrent SE function by testing associated effects on reducing parent-infant interaction and of parent psychological factors. Questionnaire responses from 327 UK-based parents of infants aged 6-24 months showed diverse usage in the amount of time spent on screen media ('screen time') and amount of parental involvement (co-sharing and co-referencing). Infants with possible SE delay experienced more screen time than those at low risk. The study tested three mediation models and found support for the displacement and not distancing hypothesis based on this community sample. While screen time predicted both SE competence and SE problems, reduced parent-infant play partially mediated the effect on SE competence. Parent depressed mood was positively linked with infant SE problems, but there was little evidence that increased screen time mediated this effect. Also, parent reflective function and attitudes toward parent-infant play were unrelated to screen time. Though longitudinal study is warranted, the findings implicate screen media usage as potentially directly and indirectly relevant when addressing infant mental health., (Copyright © 2020 Elsevier Inc. All rights reserved.)