Impaired calcium influx underlies skewed T helper cell differentiation in children with IgE-mediated food allergies.

BACKGROUND: Reasons for Th2 skewing in IgE-mediated food allergies remains unclear. Clinical observations suggest impaired T cell activation may drive Th2 responses evidenced by increased atopic manifestations in liver transplant patients on tacrolimus (a calcineurin inhibitor). We aimed to assess differentiation potential, T cell activation and calcium influx of naïve CD4+ T cells in children with IgE-mediated food allergies. METHODS: Peripheral blood mononuclear cells from infants in the Starting Time for Egg Protein (STEP) Trial were analyzed by flow cytometry to assess Th1/Th2/Treg development. Naïve CD4+ T cells from children with and without food allergies were stimulated for 7 days to assess Th1/Th2/Treg transcriptional factors and cytokines. Store operated calcium entry (SOCE) was measured in children with and without food allergies. The effect of tacrolimus on CD4+ T cell differentiation was assessed by treating stimulated naïve CD4+ T cells from healthy volunteers with tacrolimus for 7 days. RESULTS: Egg allergic infants had impaired development of IFNγ+ Th1 cells and FoxP3+ transitional CD4+ T cells compared with non-allergic infants. This parallels reduced T-bet, IFNγ and FoxP3 expression in naïve CD4+ T cells from food allergic children after in vitro culture. SOCE of naïve CD4+ T cells was impaired in food allergic children. Naïve CD4+ T cells treated with tacrolimus had reduced IFNγ, T-bet, and FoxP3, but preserved IL-4 expression. CONCLUSIONS: In children with IgE-mediated food allergies, dysregulation of T helper cell development is associated with impaired SOCE, which underlies an intrinsic impairment in Th1 and Treg differentiation. Along with tacrolimus-induced Th2 skewing, this highlights an important role of SOCE/calcineurin pathway in T helper cell differentiation.

Recommendations for eligibility criteria concerning bariatric and metabolic surgical and endoscopic procedures for obese Hong Kong adults 2024: Hong Kong Society for Metabolic and Bariatric Surgery Position Statement.

The surgical management of obesity in Hong Kong has rapidly evolved over the past 20 years. Despite increasing public awareness and demand concerning bariatric and metabolic surgery, service models generally are not standardised across bariatric practitioners. Therefore, a working group was commissioned by the Hong Kong Society for Metabolic and Bariatric Surgery to review relevant literature and provide recommendations concerning eligibility criteria for bariatric and metabolic interventions within the local population in Hong Kong. The current position statement aims to provide updated guidance regarding the indications and contraindications for bariatric surgery, metabolic surgery, and bariatric endoscopic procedures.

Asymptotic Self-Similar Blow-Up Profile for Three-Dimensional Axisymmetric Euler Equations Using Neural Networks.

Whether there exist finite-time blow-up solutions for the 2D Boussinesq and the 3D Euler equations are of fundamental importance to the field of fluid mechanics. We develop a new numerical framework, employing physics-informed neural networks, that discover, for the first time, a smooth self-similar blow-up profile for both equations. The solution itself could form the basis of a future computer-assisted proof of blow-up for both equations. In addition, we demonstrate physics-informed neural networks could be successfully applied to find unstable self-similar solutions to fluid equations by constructing the first example of an unstable self-similar solution to the Córdoba-Córdoba-Fontelos equation. We show that our numerical framework is both robust and adaptable to various other equations.

Prevalence of Prolonged Grief Disorder (PGD) among bereaved relatives in a Malaysia Palliative Care Unit (PCU).

INTRODUCTION: Prolonged grief disorder (PGD) is a diagnosis characterised by severe, persistent and disabling grief beyond 6 months post-death of a loved one. The new text revision of DSM-5 (DSM-5-TR) approved a new diagnosis PGD on March 2022. In Malaysia, PGD is not routinely screened in healthcare settings and hence goes untreated. The aim of this study is to identify prevalence and factors related to PGD among bereaved relatives whose loved ones had access to PCU services. MATERIALS AND METHODS: A cross-sectional study involving bereaved individuals in Palliative Care Unit Hospital Selayang. Participants (n=175) were recruited through telephone, and a validated tool Prolonged Grief Disorder Scale (PG-13) was asked to identify PGD. Further data collected were concomitant stressors in life and support system in the bereaved individual. RESULTS: Prevalence of PGD was 2.9% (n=5), and subthreshold PGD was 4% (n=7). A model of multiple logistic regression calculated most of the traditional risk factors were not significant except having an increased responsibility as a single parent after passing of a spouse or loved one, had 10 times increased odds of PGD (Odds Ratios: 10.93; 95% Confidence Interval: 2.937, 40.661). Otherwise, immediate family support (80%), religion (60%) and community (40%) support were the top three coping mechanisms of our PGD cohort, although they were not significant in a multiple logistic regression model. CONCLUSION: Our PGD percentage may not be as high as those of other countries, but nonetheless they exist and their needs are just as important. The authors hope that this paper may create an awareness among the healthcare clinicians about PGD in our society, for a greater access of service to understand them and better public awareness.

Links between socio-demographic characteristics and body mass index to colorectal cancer in North Borneo, Malaysia: A case-control study.

INTRODUCTION: The fourth leading cause of cancer-related mortality and morbidity worldwide is colorectal cancer (CRC). Numerous reasons have contributed to the massive rise in CRC cases, for which Asian nations differ significantly in terms of risk incidence rates. The objectives of this study were to, first, identify the socio-demographic characteristics of those of North Borneo ethnicity and body mass index (BMI) and, second, determine the association of these factors with CRC. This research will contribute to preventing this form of cancer. MATERIALS AND METHODS: This study is an analysis of a matched case-control study with a ratio of 1:2. The case group contained 206 respondents, and the control group contained 412. All CRC cases were confirmed with the histological results. The control group was matched for links between age, sex and ethnicity with CRC. The Statistical Package for Social Sciences Statistics (SPSS) IBM version 28.0 was used to conduct descriptive analysis using chi-squared testing and simple logistic regression. The statistical significance was P < 0.05. RESULT: Overall, 618 respondents took part in this survey, of which 256 (41.4%) were female and 362 (58.6%) were male. The maximum age was 76, with a mean age ± SD of 53.17 ± 11.4. Those of Bajau ethnicity comprised 24.6% (152) of the population, followed by Dusun with 22.8% (141), Kadazan with 17.6% (109%), other North Borneo ethnic groups with 15.5% (96), Bugis with 9.7% (60), Brunei with 4.4% (27) and other predominant races with 5.3% (33). Regression analyses revealed that the incidence of CRC in North Borneo, Malaysia, was substantially correlated with income, occupation, other linked diseases and BMI. CONCLUSION: Various risk factors are linked to CRC, based on the findings related to socio-demographic characteristics and BMI. Therefore, to lower the nationwide prevalence of CRC, national public health campaigns should include collaboration with the regional authorities to highlight the incidence and risk factors of CRC based on ethnicity.

Combined effect of Photorhabdus luminescens and Bacillus thuringiensis subsp. aizawai on Plutella xylostella.

In this study, we evaluated a new biopesticide containing different combinations of Photorhabdus luminescens (ATCC 29,999; Pl) and Bacillus thuringiensis subsp. aizawai (Bt) to leverage their insecticidal activity against Plutella xylostella. Mixtures containing proteins of various sizes were assayed to determine which combination of the two bacteria would yield the maximum insecticidal activity. A histopathologic slide revealed vacuole formations and rifts near the apical membrane (a symptom of Bt) and severe thinning of the intestinal wall (a symptom of Pl). When the two bacteria were cultured separately and then mixed, the insecticidal activity of the treatment reached 83.33% ± 8.82%. The insecticidal activity was elevated and significantly accelerated when Bt was mixed with both the Pl supernatant and the isolated protein with a molecular mass [Formula: see text] 100 kDa of Pl. These results highlight the potential of Pl as a potent bioinsecticide to economically and sustainably control Pl. xylostella and other lepidopteran pests. KEY POINTS: • Growth inhibition by Bacillus thuringiensis exerted a significant effect on insecticidal activity. • Large Photorhabdus luminescens proteins can accelerate the synergistic insecticidal effect on Plutella xylostella.

Imaging considerations for salvage surgery in nasopharyngeal carcinoma: what surgeons need to know.

Nasopharyngeal carcinoma is frequently an undifferentiated squamous cell carcinoma, which is primarily treated with radiotherapy with or without chemotherapy; however, for residual or recurrent cancer, salvage surgery is the treatment of choice for resectable disease because it reduces the significant morbidity associated with re-irradiation. This review highlights the current surgical approach, mapping the extent of disease with an emphasis on magnetic resonance imaging (MRI) and integrated positron-emission tomography (PET)/computed tomography (CT), imaging features that determine operability for nasopharyngectomy and neck dissection, and need for a succinct radiological report and multidisciplinary team discussion, which are of paramount importance for successful surgical planning.

Visual-auditory interactions on explicit and implicit information processing.

Interactions among sensory information are important for generating a coherent percept of the external world. Facilitation and inhibition effects in cross-modal perception have been widely studied for decades. The present study tried to confirm the interaction effects between sensory information in a bimodal context and explore these influences when part of the sensory information was presented without participants' subjective awareness. A total of 40 undergraduate participants were recruited in this mixed design study. Participants were required to count the flashing of the black circle (visual task) or the presentation frequency of the beep sound (auditory task) with the presence of either congruent or incongruent sensory signals in the background. Participants in the explicit group generally performed more accurately and also faster with the congruent stimuli than with the incongruent stimuli. Performance accuracy in the visual task in the implicit group was affected by the non-target sound signals which were presented beneath participants' subjective awareness. The better performance yielded in the auditory task than in the visual task was explained by the appropriateness of the auditory stimulation to the task nature. In addition, the supportive findings regarding processing without awareness should be interpreted with caution.

[Evaluation of severity and prognosis of acute pancreatitis by CT severity index and modified CT severity index].

Objectives: To explore the role of computed tomography (CT) severity index (CTSI) and modified CT severity index (MCTSI) in assessing the severity of acute pancreatitis (AP) under the revised Atlanta classification (RAC) and predicting the clinical prognosis. Methods: Based on the prospectively entered AP database, the clinical data of consecutive adult AP inpatients admitted to the Department of Gastroenterology of the First Affiliated Hospital of Nanchang University from January 2012 to December 2020 were retrospectively screened. The imaging data were independently evaluated by two radiologists and entered to the database to calculate the CTSI and MCTSI scores. Their relationship with the difference of RAC severity grade and clinical prognosis was analyzed. Compared with Acute Physiology and Chronic Health Assessment Ⅱ (APACHE Ⅱ) score, the receiver operating characteristic curve was used to evaluate the predictive value of CTSI and MCTSI scores for persistent organ failure and infectious pancreatic necrosis (IPN). Results: A total of 2 612 patients with AP, aged (50±15) years, were included in the study, including 1 547 males (59.2%) and 1 065 females (40.8%). According to RAC standard, AP was divided into 699 cases (26.8%) of mild pancreatitis (MAP), 1 098 cases (42.0%) of moderately severe pancreatitis (MSAP), and 815 cases (31.2%) of severe pancreatitis (SAP). MCTSI judged AP severity similarly to RAC, with 668 cases of MAP (25.6%), 1 207 cases of MSAP (46.2%) and 737 cases of SAP (28.2%), while CTSI judged SAP patients less(400 cases, 15.3%). The severity of AP determined by CTSI and MCTSI scores was significantly correlated with clinical prognosis (r=0.06-0.43, all P<0.05). Compared with APACHE Ⅱ score, CTSI had the highest area under the curve (AUC) for predicting IPN (AUC=0.85, 95%CI: 0.83-0.87), followed by MCTSI (AUC=0.82, 95%CI: 0.80-0.85). APACHE Ⅱ was more accurate in predicting persistent organ failure than CTSI and MCTSI scores,with AUC of 0.73 (95%CI: 0.71-0.75), 0.72 (95%CI: 0.70-0.74) and 0.72 (95%CI: 0.70-0.74), respectively. Conclusions: AP severity judged by MCTSI is consistent with RAC, and SAP patients judged by CTSI are less than RAC. CTSI and MCTSI are significantly correlated with clinical prognosis. CTSI and MCTSI have higher accuracy in predicting IPN, but lower accuracy in predicting persistent organ failure than APACHE Ⅱ.

Identification of proteins associated with development of metastasis from cutaneous squamous cell carcinomas (cSCCs) via proteomic analysis of primary cSCCs.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers capable of metastasizing. Proteomic analysis of cSCCs can provide insight into the biological processes responsible for metastasis, as well as future therapeutic targets and prognostic biomarkers. OBJECTIVES: To identify proteins associated with development of metastasis in cSCC. METHODS: A proteomic-based approach was employed on 105 completely excised, primary cSCCs, comprising 52 that had metastasized (P-M) and 53 that had not metastasized at 5 years post-surgery (P-NM). Formalin-fixed, paraffin-embedded cSCCs were microdissected and subjected to proteomic profiling after one-dimensional (1D), and separately two-dimensional (2D), liquid chromatography fractionation. RESULTS: A discovery set of 24 P-Ms and 24 P-NMs showed 144 significantly differentially expressed proteins, including 33 proteins identified via both 1D and 2D separation, between P-Ms and P-NMs. Several differentially expressed proteins were also associated with survival in SCCs of other organs. The findings were verified by multiple reaction monitoring on six peptides from two proteins, annexin A5 (ANXA5) and dolichyl-diphosphooligosaccharide-protein glycosyltransferase noncatalytic subunit (DDOST), in the discovery group and validated on a separate cohort (n = 57). Increased expression of ANXA5 and DDOST was associated with reduced time to metastasis in cSCC and decreased survival in cervical and oropharyngeal cancer. A prediction model using ANXA5 and DDOST had an area under the curve of 0·93 (confidence interval 0·83-1·00), an accuracy of 91·2% and higher sensitivity and specificity than cSCC staging systems currently in clinical use. CONCLUSIONS: This study highlights that increased expression of two proteins, ANXA5 and DDOST, is significantly associated with poorer clinical outcomes in cSCC.