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Daryl Jian An Tan,1 Rehena Sultana,2 Sheryl Yu Xuan Chow,3 Chin Wen Tan,1,4 Hon Sen Tan,1,4 Helen Yu Chen,5,6 Tze-Ern Chua,5,6 Ban Leong Sng1,4 1Department of Women’s Anesthesia, KK Women’s and Children’s Hospital, Singapore, Singapore; 2Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore; 3Duke-NUS Medical School, Singapore, Singapore; 4Anaesthesiology and Perioperative Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore; 5Department of Psychological Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore; 6Paediatrics Academic Clinical Program, Duke-NUS Medical School, Singapore, SingaporeCorrespondence: Chin Wen Tan, Department of Women’s Anesthesia, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore, Singapore, Tel +65 6394 6486, Fax +65 62912661, Email tan.chin.wen@kkh.com.sgPurpose: This study aimed to validate a proposed association model previously published to determine the clinical relevance of pre-operative determinants in the development of PND after Cesarean delivery (CD).Patients and Methods: Parturients undergoing elective CD under neuraxial anesthesia were recruited for a prospective cohort study between Oct 2021 and Oct 2022 at KK Women’s and Children’s Hospital, Singapore. Predelivery pain, psychological and mechanical temporal summation, and demographic data were recorded. A follow-up survey was conducted at 6 to 10 weeks after CD. The primary outcome was the incidence of PND, defined as an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 10.Results: A total of 180 patients were recruited for validation. PND 6 to 10 weeks post-delivery occurred in 18.9% of recruited parturients. Multivariate regression analyses showed that higher pre-operative CSI scores (p=0.0156), higher anxiety levels about upcoming surgery (p=0.0429), increased pre-operative pain scores on movement (p=0.0110), and higher pre-operative HADS subscale scores on anxiety (p=0.0041) were independently associated with the development of PND weeks post-CD. Lower anticipation of pain medication needs (p=0.0038) was independently associated with the development of PND post-CD. The area under curve (AUC) of this multivariable model (training cohort), internal cross validation (training cohort) and external cross validation (validation cohort) were 0.818 (95% CI, 0.746 to 0.889), 0.785 (95% CI, 0.707 to 0.864) and 0.604 (95% CI, 0.497 to 0.710) respectively.Conclusion: The proposed model performed well in a local population. Further refinement is necessary to test the proposed model in populations with social and cultural differences.Keywords: anxiety, obstetrics, pain, postnatal depression

Xiu Ling Jacqueline Sim,1 Chin Wen Tan,2,3 Cheng Teng Yeam,4 Hon Sen Tan,2,3 Rehena Sultana,5 Ban Leong Sng2,3 1Department of Anesthesiology, Singapore General Hospital, Singapore, Singapore; 2Department of Women’s Anesthesia, KK Women’s and Children’s Hospital, Singapore, Singapore; 3Anesthesiology and Perioperative Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore; 4MOH Holdings, Singapore, Singapore; 5Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore, SingaporeCorrespondence: Ban Leong Sng Tel +65 6394 1081Fax +65 6291 2661Email sng.ban.leong@singhealth.com.sgBackground: Labor pain is a variable and complex experience with both sensory and affective components. Pain catastrophizing tendencies are predictive of increased distress during labor. Likewise, pain severity has important associations with increased depressive symptoms in mothers, with consequences on perinatal and infant outcomes. Hence, we investigated the association between increased early labor pain with both pre-delivery pain catastrophizing and depressive states.Methods: We recruited nulliparous women who had requested labor epidural analgesia. Pre-delivery questionnaires including short-form McGill pain questionnaire– 2 (SF-MPQ-2), pain catastrophizing scale (PCS), and Edinburgh postnatal depression score (EPDS) were administered.Results: A total of 712 women completed the pre-delivery questionnaires. There was a significant association between SF-MPQ-2 neuropathic subscale and EPDS ≥ 10 (unadjusted OR 1.74, 95% CI 1.11– 2.73, p = 0.0161), as well as PCS ≥ 25 (unadjusted OR 1.55, 95% CI 1.06– 2.26, p = 0.0244). SF-MPQ-2 sensory intermittent subscale and EPDS ≥ 10 (unadjusted OR 2.02, 95% CI 1.34– 3.03, p = 0.0007), and PCS ≥ 25 (unadjusted OR 1.59, 95% CI 1.14– 2.23, p = 0.0069) also showed significant association.Conclusion: Increased sensory intermittent and neuropathic subsets of early labor pain are significantly correlated with increased pre-delivery pain catastrophizing and depressive states in nulliparous women. This positive association may be useful for pre-delivery risk stratification for early interventions towards a more holistic care management.Keywords: labor pain, pain catastrophizing, pre-delivery depression, survey

Chin Wen Tan,1,2 Hon Sen Tan,1,2 Rehena Sultana,3 Anne Chui,4 Tze-Ern Chua,5,6 Helen Chen,5,6 Ban Leong Sng1,2 1Department of Women’s Anesthesia, KK Women’s and Children’s Hospital, Singapore; 2Anesthesiology and Perioperative Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore; 3Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore; 4Lee Kong Chian School of Medicine, Singapore; 5Department of Psychological Medicine, KK Women’s and Children’s Hospital, Singapore; 6Pediatrics Academic Clinical Program, Duke-NUS Medical School, SingaporeCorrespondence: Ban Leong Sng Tel +65 6394 1081Fax +65 62912661Email sng.ban.leong@singhealth.com.sgPurpose: There is limited knowledge on the relationship between postnatal depression and childbirth pain characteristics associated with childbirth. We investigated whether the characteristics of childbirth pain, as assessed by Short-form-McGill Pain Questionnaire-2 (SF-MPQ-2), were associated with postnatal anxiety and depressive disorders.Patients and Methods: Nulliparous parturients who received labor epidural analgesia (LEA) and delivered in our institution were invited to have a Mini-International Neuropsychiatric Interview (MINI) assessment following their 5– 9 weeks post-delivery follow-up phone survey of a larger study. Parturients’ demographics, pre-delivery questionnaires on pain and psychological vulnerabilities, LEA data, maternal and neonatal outcomes, postnatal follow-up survey on pain and psychological vulnerabilities, pain and breastfeeding were collected accordingly. The primary outcome was the binary variable (yes/no) of the presence of postnatal depression and/or anxiety disorders based on the post-delivery MINI assessment.Results: Among the 107 parturients who participated in the post-delivery MINI assessment, a total of 40 (42.5%) patients were found to have postnatal anxiety and depressive disorders. A greater pre-delivery SF-MPQ-2 neuropathic pain mean subscale score (adjusted odds ratio (OR) 1.32, 95% CI 1.00– 1.73, p=0.0482) and greater post-delivery Edinburgh Postnatal Depression Scale (EPDS) at 5– 9 weeks post-delivery (adjusted OR 1.30, 95% CI 1.13– 1.50, p=0.0002) were independently associated with the presence of postnatal anxiety and/or depressive disorders (receiver operating characteristic (ROC) = 0.7489).Conclusion: Patients with greater pre-delivery neuropathic pain and higher EPDS scores at 5– 9 weeks post-delivery are more likely to have postnatal depression and/or anxiety disorders, suggesting possible associations between pain and psychological vulnerability in the development of postnatal mental disorders.Keywords: neuropathic pain, postnatal depression, anxiety, pain vulnerability

Hon Sen Tan,1 Ashraf S Habib2 1Department of Women’s Anesthesia, KK Women’s and Children’s Hospital, 229899, Singapore; 2Department of Anesthesiology, Division of Women’s Anesthesia, Duke University Medical Center, Durham, NC, 27710, USACorrespondence: Ashraf S HabibDepartment of Anesthesiology, Division of Women’s Anesthesia, Duke University Medical Center, Box 3094, Durham, NC, 27710, USATel +1 9196682024Email ashraf.habib@duke.eduAbstract: Optimal pain relief requires a balance between adequate analgesia and risk of adverse effects. Opioids remain the cornerstone for managing moderate to severe pain, but are associated with opioid-induced respiratory depression (OIRD) and gastrointestinal complications. Opioids exert their analgesic effects predominantly via G-protein signaling, however, adverse effects including OIRD are mediated by the β-arrestin pathway. Oliceridine is the first of a new class of biased opioid agonists that preferentially activate G-protein signaling over β-arrestin, which would theoretically improve analgesia and reduce the risk of adverse effects. Oliceridine is approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe acute pain. The efficacy of Oliceridine was mainly established in two randomized controlled Phase III clinical trials of patients experiencing moderate to severe pain after bunionectomy (APOLLO-1) and abdominoplasty (APOLLO-2). The results of the APOLLO studies demonstrate that Oliceridine, when administered via patient-controlled analgesia (PCA) demand boluses of 0.35mg and 0.5mg, provides superior analgesia compared to placebo, and is equianalgesic to PCA morphine 1mg demand boluses, without significant difference in the incidence of respiratory complications. In a more pragmatic trial of surgical and non-surgical patients, the ATHENA observational cohort study reported rapid onset of analgesia with Oliceridine given with or without multimodal analgesia. However, these studies were designed to evaluate analgesic efficacy, and it is still uncertain if Oliceridine has a better safety profile than conventional opioids. Although several post hoc analyses of pooled data from the APOLLO and ATHENA trials reported that Oliceridine was associated with lower OIRD and gastrointestinal complications compared to morphine, prospective studies are needed to elucidate if biased agonists such as Oliceridine reduce the risk of adverse effects compared to conventional opioids.Keywords: TRV130, biased ligand, opioid agonist, mu-opioid receptor

Hon Sen Tan,1 Rehena Sultana,2 Nian-Lin Reena Han,3 Chin Wen Tan,1,4 Alex Tiong Heng Sia,1,4 Ban Leong Sng1,4 1Department of Women’s Anaesthesia, KK Women’s and Children’s Hospital, Singapore; 2Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore; 3Division of Clinical Support Services, KK Women’s and Children’s Hospital, Singapore; 4Anesthesiology and Perioperative Sciences Academic Clinical Program, SingHealth-Duke-NUS Medical School, SingaporeCorrespondence: Ban Leong SngDepartment of Women’s Anaesthesia, KK Women’s and Children’s Hospital, 100 Bukit Timah Road 229899, SingaporeTel +65 6394 1077Email sng.ban.leong@singhealth.com.sgPurpose: Hysterectomy is associated with a high incidence of chronic post-hysterectomy pain (CPHP). Pain catastrophizing, a negative cognitive-affective response to pain, is associated with various pain disorders but its role in CPHP is unclear. We aimed to determine the association of high preoperative pain catastrophizing with CPHP development and functional impairment 4 months after surgery.Patients and Methods: Secondary analysis of a prospective cohort study of women undergoing abdominal/laparoscopic hysterectomy to investigate the association between high pain catastrophizing (pain catastrophizing scale, PCS≥ 20) with CPHP and associated functional impairment (defined as impairment with standing for ≥ 30 minutes, sitting for ≥ 30 minutes, or walking up or down stairs). CPHP and functional impairment were assessed via 4- and 6-month phone surveys.Results: Of 216 patients, 72 (33.3%) had high PCS, with mean (SD) of 30.0 (7.9). In contrast, 144 (66.7%) patients had low PCS, with mean (SD) of 9.0 (4.7). At 4 months, 26/63 (41.3%) patients in the high PCS group developed CPHP, compared to 24/109 (22.0%) in the low PCS group. At 6 months, 14/53 (26.4%) high PCS patients developed CPHP, compared to 10/97 (10.3%) patients with low PCS. High PCS was independently associated with CPHP at 4 months (OR 2.49 [95% CI 1.27 to 4.89], p=0.0082) and 6 months (OR 3.12 [95% CI 1.28 to 7.64], p=0.0126) but was not associated with functional impairment. High PCS≥ 20, presence of evoked mechanical temporal summation (MTS), and history of abdominal/pelvic surgery predict CPHP at 4 months with area under the curve (AUC) of 0.69. Similarly, PCS≥ 20 and increasing MTS magnitude predicted CPHP at 6 months with AUC of 0.76.Conclusion: High PCS was independently associated with CPHP. Future studies should identify other CPHP associated factors to formulate a risk-prediction model and investigate the effectiveness of early intervention for pain catastrophizers in improving pain-related outcomes.Keywords: pain catastrophizing scale, mechanical temporal summation

Raba Thapa,1 Shankar Khanal,2 Hendra Stevie Tan,3 Suman Shumsher Thapa,1 Gerardus Hermanus Maria Bartholomeus van Rens3 1Tilganga Institute of Ophthalmology, Kathmandu, Nepal; 2Central Department of Statistics, Tribhuvan University, Kirtipur, Nepal; 3Department of Ophthalmology, Amsterdam University Medical Center, Vrije University Amsterdam, Amsterdam, the NetherlandsCorrespondence: Raba ThapaTilganga Institute of Ophthalmology, Bagmati Bridge, Kathmandu, NepalTel +977-1-4493775Fax +977-1-4474937Email rabathapa@live.comIntroduction: Retinal diseases are an emerging cause of visual impairment in the developing world. The aim of this study was to explore the prevalence, pattern, and risk factors of retinal diseases in Nepal.Methods: This is a population-based, cross-sectional study conducted from 2013 to 2015. The sample size was 2100 subjects age 60 years and above from 30 clusters of Bhaktapur district, Nepal. Detailed history, visual acuity, and anterior and posterior segment examinations were performed. Blood sugar and blood pressure were measured.Results: Complete information was available for 1860 (88.57%) subjects. Mean age was 69.64± 7.31 years, ranging from 60 to 95 years. The prevalence of any retinal disorder was 52.37% (95% confidence interval (CI): 50.07– 54.66%). The prevalence of retinal disorders increased with ageing: 51.26% between 60 and 69 years and 53.05% among those age 80 years and above. Age-related macular degeneration (AMD) was the most common retinal disease (35.43%), followed by hypertensive retinopathy (4.35%), epiretinal membrane (ERM) (3.66%), branch retinal vein occlusion (BRVO) (2.90%), and diabetic retinopathy (DR) (2.15%). Other rare retinal disorders included myopic fundus (0.86%), chorioretinal scar (0.54%), retinal holes (0.32%), retinitis pigmentosa (0.32%), retinal detachment (0.16%), and coloboma (0.11%). In multivariate logistic regression analysis, those with prior cataract surgery (odds ratio (OR), 1.71; 95% CI: 1.32– 2.22, p < 0.001) and systemic hypertension (OR, 1.21; 95% CI: 1.001– 1.47, p = 0.049) had significantly increased retinal disorders.Conclusion: Prevalence of retinal disorder was 52.37% at age 60 years and above. AMD, hypertensive retinopathy, ERM, BRVO, and DR were the most common retinal disorders. Retinal disorders increased with ageing. Retinal disorders were found associated with hypertension and prior cataract surgery. Timely screening, control of blood sugar and high blood pressure, and regular eye check-ups could help to save vision from retinal diseases.Keywords: retinal diseases, age-related macular degeneration, hypertensive retinopathy, diabetic retinopathy, retinal vein occlusion, epiretinal membrane

Ene-Choo Tan,1,2 Hwee-Woon Lim,1 Tze-Ern Chua,2,3 Hui-San Tan,1 Theresa MY Lee,2,3 Helen Y Chen2,3 1KK Research Centre, KK Women’s and Children’s Hospital, Singapore, Singapore; 2Paediatrics Academic Clinical Programme, SingHealth Duke-NUS Medical School, Singapore, Singapore; 3Department of Psychological Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore Objectives: Depressive symptoms are common during pregnancy and after childbirth. Estrogen levels fluctuate greatly during the course of pregnancy and may contribute to mood instability. The first aim of this case–control study was to investigate whether variants in the two estrogen receptor genes might contribute to the genetic susceptibility to pregnancy-related depression using controls that were screened for postnatal depression. The second aim was to uncover new variants in the two estrogen receptor genes. Patients and methods: Our study sample comprised 554 control subjects who had Edinburgh Postnatal Depression Scale (EPDS) scores below 7 at postnatal screening, and 159 patients with clinically diagnosed pregnancy-related depression. They were genotyped for four single-nucleotide polymorphisms (SNPs) and a dinucleotide repeat in the two genes: estrogen receptor α (ESR1) and estrogen receptor β (ESR2). Fifty-six cases with personal and/or family history of depression of psychiatric disorders were selected for resequencing of the two genes. Results: There was no statistically significant association with perinatal depression for all five variants. However, there was a trend toward higher frequencies of the genotypes associated with higher risk of depression for rs2077647 and rs4986938 in the case group. From resequencing, two novel ESR1 variants were identified from two different patients. Conclusion: Our study that used screened controls with low EPDS scores and cases with clinically diagnosed pregnancy-related depression could not replicate the association with depression for any of the SNPs for both genotype and allele frequencies. Two novel SNPs were identified and could be further investigated in a larger sample set. Keywords: childbirth, depression, hormone, single-nucleotide polymorphism, postpartum

Daphne L Mourits,1 Dyonne T Hartong,1 Andries E Budding,2 Machteld I Bosscha,1 H Stevie Tan,1 Annette C Moll1 1Department of Ophthalmology, VU University Medical Center, 2Department of Microbiology, Academic Medical Center, Amsterdam, the Netherlands Purpose: To investigate the causes and treatment options for socket discharge and infection in patients enucleated for retinoblastoma (Rb). Methods: A questionnaire was filled out by (parents of) ocular prosthesis-wearing patients with a history of enucleation as treatment for Rb. We collected data on patients’ characteristics, cleaning habits of the prosthesis, frequency of socket irritation, discharge, and infection, and use of antibiotics. With ordinal logistic regression analysis, factors related to the outcome parameters (frequency of irritation, mucoid and purulent discharge) were identified. In a subset of young asymptomatic and symptomatic patients, a swab culture of the socket was performed to determine the presence of microorganisms. Results: A total of 186 patients or their parents (mean age of the patients: 17.3 years, ranging from 0.8 to 88.3 years) filled out the questionnaire. Irritation, mucoid discharge, and purulent discharge were frequently (once a month or more often) experienced in 75 (39.5%), 127 (66.8%), and 15 (13.2%) sockets, respectively. Younger age was associated with a higher frequency of mucoid and purulent discharge. Radiation therapy, chemotherapy, gender, age at surgery, cleaning frequency, and nocturnal wear were not associated with the outcome parameters. In a subgroup of 26 patients, the sockets were swabbed and cultured. All symptomatic patients had a positive bacterial culture versus 15% (2/13) of the asymptomatic patients (P

Abstract Background Epidemiological surveillance of infectious diseases through the mandatory-reporting system is crucial in the planning and evaluation of disease control and prevention program. This study investigated the reporting behavior, knowledge, and attitude to reporting communicable disease in private doctors in Taiwan. The differences between the reporting and non-reporting doctors were also explored. Methods A total of 1250 clinics were randomly sampled nationwide by a 2-stage process. Data were collected from 1093 private doctors (87.4% response rate) using a self-administered structured questionnaire. Four hundred and six (37.2%) doctors reported having diagnosed reportable communicable diseases. Among them, 340 (83.5%) have the experiences of reporting. Results The most common reasons for not reporting were "do not want to violate the patient's privacy", "reporting procedure is troublesome", and "not sure whether the diagnosed disease is reportable". Significantly higher proportions of the non-reporting doctors considered the reporting system inconvenient or were not familiar with the system. The highest percentage (65.2%) of the non-reporting doctors considered that a simplified reporting procedure, among all measures, would increase their willingness to report. In addition, a significantly higher proportion of the non-reporting doctors would increase their willingness to report if there has been a good reward for reporting or a penalty for not reporting. Conclusion The most effective way to improve reporting rate may be to modify doctor's attitude to disease reporting. The development of a convenient and widely-accepted reporting system and the establishment of a reward/penalty system may be essential in improving disease reporting compliance in private doctors.

Acinetobacter baumannii, a top-priority WHO pathogen, causes life-threatening infections in immunocompromised patients, leading to prolonged hospitalisation and high mortality. Here, we used the Galleria mellonella model to investigate community strain C98 (Ab-C98) virulence via transcriptomic analysis. Ab-C98 showed greater killing and faster colonisation in larvae than the clinical reference strain (ATCC BAA1605). Genes in three iron clusters, acinetobactin, baumannoferrin and the Feo system, were significantly up-regulated. Targeted knockout of siderophore genes (basC, bfnD, and the gene encoding isochorismatase) significantly increased the survival of infected larvae by at least 35.16%, identifying these genes as potential targets for developing anti-virulence agents against A. baumannii., (© 2024 Federation of European Biochemical Societies.)

Cross peaks on 2D optical spectra are indicative of interactions between molecular excitonic states. Currently, the two conventional assignments of cross peaks are direct coupling and population transfer between excitonic states. Here, we show that there is another possible source of cross peaks. We theoretically demonstrate that for a model comprising two nondirectly interacting excitons or two-level systems (TLSs), cross peaks can arise if there is a complex-valued or quantum frequency-gap cross-correlation function between the two TLSs. Considering only real-valued or classical cross-correlation functions will result in no cross peaks. We derive and validate the mathematical expressions describing such cross peaks. We then simulate the 2D electronic spectra of an example model system comprising nondirectly interacting TLSs whose quantum cross-correlation functions arise from coupling to a common overdamped Brownian oscillator mode. We show that there are clear observational differences between such quantum correlation cross peaks with conventional direct coupling and population transfer cross peaks.

Despite being a major human pathogen, limited studies have reported RNA modifications in Acinetobacter baumannii . These post-transcriptional modifications play crucial regulatory roles in bacteria and have also been shown to modulate bacterial virulence. Using nanopore sequencing, we characterized RNA modifications in a virulent A. baumannii strain (Ab-C98) under free-living (mid-exponential phase in vitro culture) and during an early stage of infection (3 h post-infection) in Galleria mellonella larvae. Analysis revealed that m 5 C methylations are essential for ribosome synthesis, while m 6 A and Ψ are involved in metabolic pathways and translation processes. Iron-chelating genes exbD (m 5 C and m 6 A) and feoB (m 6 A and Ψ) and RNA polymerase subunit rpoC (m 6 A and Ψ) were selectively modified during infection. This first transcriptome-wide study highlights the potential regulatory roles of m 5 C, m 6 A and Ψ modifications in A. baumannii during infection.

Background: As we navigate towards integrating deep learning methods in the real clinic, a safety concern lies in whether and how the model can express its own uncertainty when making predictions. In this work, we present a novel application of an uncertainty-quantification framework called Deep Evidential Learning in the domain of radiotherapy dose prediction., Method: Using medical images of the Open Knowledge-Based Planning Challenge dataset, we found that this model can be effectively harnessed to yield uncertainty estimates that inherited correlations with prediction errors upon completion of network training. This was achieved only after reformulating the original loss function for a stable implementation., Results: We found that (i) epistemic uncertainty was highly correlated with prediction errors, with various association indices comparable or stronger than those for Monte-Carlo Dropout and Deep Ensemble methods, (ii) the median error varied with uncertainty threshold much more linearly for epistemic uncertainty in Deep Evidential Learning relative to these other two conventional frameworks, indicative of a more uniformly calibrated sensitivity to model errors, (iii) relative to epistemic uncertainty, aleatoric uncertainty demonstrated a more significant shift in its distribution in response to Gaussian noise added to CT intensity, compatible with its interpretation as reflecting data noise., Conclusion: Collectively, our results suggest that Deep Evidential Learning is a promising approach that can endow deep-learning models in radiotherapy dose prediction with statistical robustness. We have also demonstrated how this framework leads to uncertainty heatmaps that correlate strongly with model errors, and how it can be used to equip the predicted Dose-Volume-Histograms with confidence intervals., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To observe the clinical efficacy of meridian massage in the treatment of lumbar disc herniation(LDH)., Methods: Between July 2020 and April 2023, 82 patients with lumbar disc herniation were selected, including 58 males and 24 females, aged from 23 to 55 years old with an average of (43.76±6.64) years old. According to the different treatment methods, they were divided into observation group and control group with 41 cases in each group. The control group was treated with routine treatment, and the observation group was treated with meridian massage on the basis of routine treatment. In the control group, there were 30 males and 11 females;aged from 22 to 52 years old with an average of (42.27±9.34) years old;the Body mass index (BMI) ranged from 19 to 28 kg·m -2 with an average of(23.82±1.08) kg·m -2 ;the course of disease ranged from 0.5 to 3.0 years (2.40±0.48) years. There were 28 cases in L 4,5 segment and 13 cases in L 5 S 1 segment. In the observation group, there were 28 males and 13 females;the age ranged from 19 to 54 years old (42.19±9.26) years old;the BMI ranged from 18 to 29 kg·m -2 with an average of(23.73±1.15) kg·m -2 ;the course of disease ranged from 0.6 to 2.8 with an average of(2.56±0.45) years;there were 26 cases in L 4,5 segment and 15 cases in L 5 S 1 segment. Visual analogue scale(VAS), Oswestry disability index(ODI), M-JOA score and TCM syndrome score were measured before and after 3 courses of treatment, and the clinical efficacy was evaluated by the standard of curative effect evaluation., Results: After treatment, VAS [(3.24±1.45) vs(4.46±0.64)], ODI [(11.45±1.98)% vs (17.21±2.74)%] and TCM symptom score [(2.03±0.27) vs (3.99± 0.54)] of the observation group were lower than those of the control group. The score of M-JOA [(23.43±2.61) vs (19.37±1.62)] increased ( P <0.05). The scores of VAS, ODI and TCM symptoms in the observation group were lower than those in the control group, while the scores of M-JOA were higher than those in the control group ( P <0.05)., Conclusion: Meridian massage is effective in the treatment of LDH, which can effectivelyrelieve low back pain, improve clinical symptoms and increaselumbar function, which is worthy of clinical promotion.

The use of artificial intelligence (AI) in obstetric anaesthesiology shows great potential in enhancing our practice and delivery of care. In this narrative review, we summarise the current applications of AI in four key areas of obstetric anaesthesiology (perioperative care, neuraxial procedures, labour analgesia and obstetric critical care), where AI has been employed to varying degrees for decision support, event prediction, risk stratification and procedural assistance. We also identify gaps in current practice and propose areas for further research. While promising, AI cannot replace the expertise and clinical judgement of a trained obstetric anaesthesiologist. It should, instead, be viewed as a valuable tool to facilitate and support our practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To investigate if changes in vessel density (VD) and the foveal avascular zone (FAZ) occur in the preclinical phase of Alzheimer's disease (pAD) over time., Methods: Optical coherence tomography angiography (OCTA) was used to image VD and FAZ at baseline and for a follow-up period of 2 years. Positron emission tomography (PET) was used to determine the amyloid beta (Aβ) status of participants., Results: The VD and FAZ of 148 participants (54% female) were analyzed at baseline and follow-up (mean time between measurements, 2.24 ± 0.35 years). The mean age of the participants was 68.3 ± 6.0 years at baseline and 70.3 ± 5.9 years at follow-up. Participants were divided into three groups: control group, participants who had negative Aβ status at both measurements (Aβ-, n = 116); converter group, participants who transitioned from negative to positive between baseline and follow-up (Aβ-+, n = 18); and participants who were consistently positive at both visits (Aβ++, n = 14). The VD of both Aβ+ groups demonstrated non-significant increases over time in both macula and optic nerve head (ONH) regions. The Aβ- group was found to be significantly higher in both ONH and macular regions. The VD of the Aβ++ group was significantly higher in the macula inner and outer rings compared to the Aβ-+ and Aβ- groups. No significant change was found in FAZ values over time., Conclusions: Alterations in VD seem to manifest already in pAD, exhibiting distinct variations between the ONH and macula. Further longitudinal studies with a longer follow-up design and known amyloid pathology should be undertaken to validate these observations.

Acute pain management requires balancing analgesia with adverse effects risk. The voltage-gated sodium channel NaV1.8 plays an important role in pain physiology, and its inhibition was shown to have analgesic effects. VX-548 is a new oral NaV1.8-specific inhibitor that received United States Food and Drug Administration Fast Track and Breakthrough Therapy designations. Its efficacy was demonstrated in two Phase II trials of patients who underwent abdominoplasty and bunionectomy. These showed that VX-548, when given as an oral loading dose of 100 mg followed by 50 mg 12-hly, significantly decreased pain scores compared with placebo. Similarly, two Phase III trials of patients who underwent abdominoplasty and bunionectomy comparing VX-548 with hydrocodone bitartrate-acetaminophen and placebo reported significantly reduced pain scores compared with placebo, but no improvement compared with hydrocodone bitartrate-acetaminophen. Evidence from Phase II and III trials suggest that VX-548 is well-tolerated, with headache, nausea, constipation and dizziness being the most common adverse effects. However, the safety of prolonged VX-548 administration is uncertain; a Phase II trial of patients with diabetic neuropathy who received high-dose VX-548 over 12 weeks reported decreased creatinine clearance. Data pertaining to VX-548 safety and efficacy within the context of multimodal analgesia and pregnancy are also needed.

Purpose: Recent studies have reported the use of the obstetric-specific quality of recovery tool (ObsQoR-10) to assess the quality of recovery in parturients after childbirth; however, the correlation between ObsQoR-10 scores and important postpartum outcomes are unclear. The primary aim of the present study was to investigate the correlations between ObsQoR-10 scores at 24 hr after Cesarean delivery and breastfeeding, depressive symptomatology, overall health, and pain at seven days postpartum., Methods: We recruited parturients who underwent elective Cesarean delivery at KK Hospital in Singapore. Parturients provided responses to post-Cesarean questionnaires at 1) 24 hr (ObsQoR-10, EuroQol EQ-Visual Analogue Scale, Edinburgh Postnatal Depression Scale), 2) 48 hr (ObsQoR-10, EQ-Visual Analogue Scale), and 3) seven days after Cesarean delivery (ObsQoR-10, Breastfeeding Self-Efficacy Scale-Short form, EQ-Visual Analogue Scale, Edinburgh Postnatal Depression Scale, pain survey)., Results: We enrolled 222 participants, 200 (90%) of whom completed the seven-day follow-up between September 2022 and April 2023. There was limited correlation between ObsQoR-10 at 24 hr with the Edinburgh Postnatal Depression Scale (r = 0.135), EQ-Visual Analogue Scale (r = 0.158), Breastfeeding Self-Efficacy Scale-Short form (r = 0.225), and averaged pain scores (r = -0.107) at seven days postpartum. ObsQoR-10 breastfeeding sub-score at 24 hr was weakly correlated with Breastfeeding Self-Efficacy Scale-Short form at seven days postpartum (r = 0.307)., Conclusion: ObsQoR-10 at 24 hr postpartum had limited correlation with breastfeeding, depressive symptomatology, overall health, and pain at seven days., Study Registration: ClinicalTrials.gov ( NCT04989894 ); first submitted 4 July 2021., (© 2024. Canadian Anesthesiologists' Society.)

Objective: To observe the clinical efficacy of meridian massage in the treatment of cervical spondylotic radiculopathy., Methods: Sixty-four patients with cervical radiculopathy treated from March 2020 to June 2023 were divided into the observation group and the treatment group, with 32 cases in each group. The observation group received conventional treatment, including 14 males and 18 females with an average age of (41.34±7.23) years old ranging from 32 to 55 years old;the disease duration ranged from 9 to 17 months with an average of (14.23±3.56) months;C 5 and C 6 nerve root compression occurred in 12 cases, C 7 nerve root compression occurred in 17 cases, C 8 nerve root compression occurred in 3 cases. The treatment group received massage therapy on the basis of conventional treatment, including 17 males and 15 females with an average age of (40.86±6.97) years old ranging from 30 to 54 years old;the disease duration ranged from 8 to 18 months with an average of (15.43±3.48) months;C 5 and C 6 nerve root compression occurred in 14 cases, C 7 nerve root compression occurred in 16 cases, C 8 nerve root compression occurred in 2 cases. The clinical efficacy was evaluated by visual analogue scale(VAS), neck disability index(NDI) and clinical assessment scale for cervical spondylosis(CASCS) before and after 2-week treatment, and the range of motion of cervical spine was compared before and after treatment., Results: After 2-week treatment, the VAS and NDI scores of the treatment group and the observation group decreased, while the CASCS scores increased( P <0.001). After 2-week treatment, the VAS and NDI scores were lower and the CASCS scores were higher in the treatment group than those of the observation group( P <0.001). Comparing with those before treatment, the range of motion of flexion, extension, left flexion, right flexion, left rotation and right rotation after 2-week treatment increased in two groups( P <0.05). Comparing with the observation group, the range of motion of flexion, extension, left flexion, right flexion, left rotation and right rotation increased more significantly in the treatment group( P <0.05)., Conclusion: Meridian massage is effective in the treatment of cervical Spondylotic radiculopathy, which can effectively relieve neck pain, improve clinical symptoms and improve patient satisfaction.

Background: Alzheimer's disease (AD) is a common, complex and multifactorial disease that may require screening across multiple routes of referral to enable early detection and subsequent future implementation of tailored interventions. Blood- and eye-based biomarkers show promise as low-cost, scalable and patient-friendly tools for early AD detection given their ability to provide information on AD pathophysiological changes and manifestations in the retina, respectively. Eye clinics provide an intriguing real-world proof-of-concept setting to evaluate the performance of these potential AD screening tools given the intricate connections between the eye and brain, presumed enrichment for AD pathology in the aging population with eye disorders, and the potential for an accelerated diagnostic pathway for under-recognized patient groups., Methods: The BeyeOMARKER study is a prospective, observational, longitudinal cohort study aiming to include individuals visiting an eye-clinic. Inclusion criteria entail being ≥ 50 years old and having no prior dementia diagnosis. Excluded eye-conditions include traumatic insults, superficial inflammation, and conditions in surrounding structures of the eye that are not engaged in vision. The BeyeOMARKER cohort (n = 700) will undergo blood collection to assess plasma p-tau217 levels and a brief cognitive screening at the eye clinic. All participants will subsequently be invited for annual longitudinal follow-up including remotely administered cognitive screening and questionnaires. The BeyeOMARKER + cohort (n = 150), consisting of 100 plasma p-tau217 positive participants and 50 matched negative controls selected from the BeyeOMARKER cohort, will additionally undergo Aβ-PET and tau-PET, MRI, retinal imaging including hyperspectral imaging (primary), widefield imaging, optical coherence tomography (OCT) and OCT-Angiography (secondary), and cognitive and cortical vision assessments., Results: We aim to implement the current protocol between April 2024 until March 2027. Primary outcomes include the performance of plasma p-tau217 and hyperspectral retinal imaging to detect AD pathology (using Aβ- and tau-PET visual read as reference standard) and to detect cognitive decline. Initial follow-up is ~ 2 years but may be extended with additional funding., Conclusions: We envision that the BeyeOMARKER study will demonstrate the feasibility of early AD detection based on blood- and eye-based biomarkers in alternative screening settings, and will improve our understanding of the eye-brain connection., Trial Registration: The BeyeOMARKER study (Eudamed CIV ID: CIV-NL-23-09-044086; registration date: 19th of March 2024) is approved by the ethical review board of the Amsterdam UMC., (© 2024. The Author(s).)

Competing Interests: Competing interests: None declared.

Metal nanoclusters (MNCs) have outstanding fluorescence property and biocompatibility, which show widespread applications in biological analysis. Particularly, evaluation of enzyme activity with the fluorescent MNCs has been developed rapidly within the past several years. In this review, we first introduced the fluorescent mechanism of mono- and bi-metallic nanoclusters, respectively, whose interesting luminescence properties are mainly resulted from electron transfer between the lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) energy levels. Meanwhile, the charge migration within the structure occurs through ligand-metal charge transfer (LMCT) or ligand-metal-metal charge transfer (LMMCT). On such foundation, diverse enzyme activities were rigorously evaluated, including three transferases and nine hydrolases, in turn harvesting rapid research progresses within past 5 years. Finally, we summarized the design strategies for evaluating enzyme activity with the MNCs, presented the major issues and challenges remained in the relevant research, coupled by showing some improvement measures. This review will attract researchers dedicated to the studies of the MNCs and provide some constructive insights for their further applications in enzyme analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acinetobacter baumannii is a Gram-negative, opportunistic pathogen that causes nosocomial infection with a high mortality rate in immunocompromised individuals. With the frequent emergence of multidrug-resistant A. baumannii strains that have rapidly gained resistance to most antibiotics, an extensive search for an effective A. baumannii vaccine is ongoing. Over the decade, many subunit vaccine candidates were identified using reverse vaccinology and in vivo animal studies for validation. Nineteen subunit vaccine candidates with a wide range of efficacy, from 14% to 100% preclinical survival rates, were included in this review. This article provides an updated review of several outer membrane proteins (Omp) that emerged as vaccine candidates with great potential, including OmpA, Omp34, Omp22 and BamA, based on their high conservancy, antigenicity, and immune protection against A. baumannii infection. However, there is still no licenced A. baumannii vaccine currently due to several practical issues that have yet to be resolved, such as inconsistencies between validation studies, antigen variability and insolubility. Moving forward, much investigation and innovation are still required to tackle these challenges for the regulatory approval of an A. baumannii subunit vaccine, including standardisation of immunisation study parameters, improving antigen solubility and the incorporation of nucleic acid vaccine technology.

Two-dimensional electronic spectroscopy (2DES) has proven to be a highly effective technique in studying the properties of excited states and the process of excitation energy transfer in complex molecular assemblies, particularly in biological light-harvesting systems. However, the accurate simulation of 2DES for large systems still poses a challenge because of the heavy computational demands it entails. In an effort to overcome this limitation, we devised a coarse-grained 2DES method. This method encompasses the treatment of the entire system by dividing it into distinct weakly coupled segments, which are assumed to communicate predominantly through incoherent exciton transfer. We first demonstrate the efficiency of this method through simulation on a model dimer system, which demonstrates a marked improvement in calculation efficiency, with results that exhibit good concordance with reference spectra calculated with less approximate methods. Additionally, the application of this method to the light-harvesting antenna 2 (LH2) complex of purple bacteria showcases its advantages, accuracy, and limitations. Furthermore, simulating the anisotropy decay in LH2 induced by energy transfer and its comparison with experiments confirm that the method is capable of accurately describing dynamical processes in a biologically relevant system. This method presented lends itself to an extension that accounts for the effect of intrasegment relaxation processes on the 2DES spectra, which for computational efficiency are ignored in the implementation reported here. It is envisioned that the method will be employed in the future to accurately and efficiently calculate 2D spectra of more extensive systems, such as photosynthetic supercomplexes.

Objective: To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2 ) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods: A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results: A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ 2 =16.063, P< 0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion: The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.

Shigella causes shigellosis that requires antibiotic treatment in severe cases. Sublethal antibiotic concentrations can promote resistance, but their effect on antibiotic-sensitive bacteria before resistance development is unclear. This study investigated the effects of sublethal norfloxacin (NOR) challenges on a NOR-sensitive strain, Shigella sonnei UKMCC1015. Firstly, the whole genome of S. sonnei UKMCC1015 was assembled, and 45 antimicrobial resistance (AMR) genes were identified. Interestingly, transcriptomic analysis showed that low NOR levels do not change either the expression of the AMR genes or NOR targets such as gyrA . Instead, multiple ribosomal protein genes were downregulated, which could be attributed to decreased ribosomal protein promoter activity, modulated by elevated guanosine pentaphosphate and tetraphosphate (ppGpp) levels. This alarmone is involved in the bacterial stringent response during environmental stress, and it is mainly produced from the ppGpp synthetase ( relA ). Additionally, we observed that a relA overexpression (prolonged period of elevated ppGpp levels) may negatively affect the NOR tolerance of the bacteria. In conclusion, this study revealed that a NOR-sensitive strain responds differently to sublethal NOR than commonly reported in resistant strains., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

The light-harvesting complexes (LHCs) of diatoms, specifically fucoxanthin-Chl a / c binding proteins (FCPs), exhibit structural and functional diversity, as highlighted by recent structural studies of photosystem II-FCP (PSII-FCPII) supercomplexes from different diatom species. The excitation dynamics of PSII-FCPII supercomplexes isolated from the diatom Thalassiosira pseudonana was explored using time-resolved fluorescence spectroscopy and two-dimensional electronic spectroscopy at room temperature and 77 K. Energy transfer between FCPII and PSII occurred remarkably fast (<5 ps), emphasizing the efficiency of FCPII as a light-harvesting antenna. The presence of long-wavelength chlorophylls may further help concentrate excitations in the core complex and increase the efficiency of light harvesting. Structure-based calculations reveal remarkably strong excitonic couplings between chlorophylls in the FCP antenna and between FCP and the PSII core antenna that are the basis for the rapid energy transfer.

The high level of alpha-fetoprotein (AFP) expression is closely related to hepatocellular carcinoma (HCC). Herein, a dual signal ratiometric electrochemical immunosensor based on chitosan-ferrocenecarboxaldehyde-spindle gold (Chit-Fc-SAu) and Co/Fe metal-organic framework-toluidine blue/polydopamine (Co/Fe MOF-TB/PDA) was proposed for quantitative analysis of AFP. Specifically, Chit-Fc-SAu worked as a substrate to trap more primary antibodies (Ab 1 ) generating the first electrochemical signal from Fc. Thanks to the large specific surface area, the synergistic and electronic effects of Co/Fe MOF nanosheets, and the rich functional groups of PDA, Co/Fe MOF-TB/PDA could load more secondary antibodies (Ab 2 ) and signal molecules (TB) providing another amplified electrochemical signal. In the presence of AFP, Ab 1 -AFP-Ab 2 formed a sandwich structure, and as the AFP concentration increased, the peak current ratio of TB to Fc (I TB /I Fc ) also increased. The dual signal ratiometric strategy can avoid environmental signal interference and achieve signal self-calibration, thereby improving the accuracy and reproducibility of detection. After a series of exploration, this self-calibrated ratiometric immunosensor exhibited a wide linear range (0.001-200 ng mL -1 ), a low detection limit (0.34 pg mL -1 ), and good repeatability. When applied to the assay of clinical serum samples, the detection results of ratiometric sensor were consistent with that of commercial electrochemiluminescence (ECL) immunoassay, significantly superior to that of non-ratiometric sensor. The self-calibrated strategy based on ratiometric sensor helps to improve the accuracy of AFP in clinical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)