bluuebunny/crossref_metadata_2025 huggingface dataset:
The 50% effective dose of hydromorphone and morphine for epidural analgesia in the hemorrhoidectomy: a double-blind, sequential dose-finding study
Authors: Cao Xianghua , Gui Qiangjun , Wei Yujiao , Lan Lanhui , Xiao Huiling , Wen Shihong , Li Xueping
Published: January 2024

Background

Although previous studies have showed that epidural morphine can be used as a complement to local anesthetics for analgesia after postcesarean delivery under spinal anesthesia, there is little known about the analgesic dosage of epidural morphine and hydromorphone for hemorrhoidectomy. Therefore, we conducted this study to examine the potency ratio of hydromorphone to epidural morphine as well as effective analgesic dose for 50% patients (ED50) undergoing elective hemorrhoidectomy.

Methods

80 patients under elective hemorrhoidectomy with combined spinal and epidural anesthesia(CSEA) in department of anesthesia, Dongguan Tungwah hospital. To assess the ED50, patients were treated with epidural morphine or epidural hydromorphone randomly using a biased coin method-determined dose with a sequential allocation procedure. Following surgery, standardized multimodal analgesia was administered to all patients. A pain response score of ≤ 3 (on a scale of 0–10) was determined to be the effective dose after 24 h following CSEA. The ED50 in both groups were determined using the probit regression and isotonic regression method. We also measured pain intensity by patient interview using a 10 point verbal numeric rating scale prospectively at 6, 12 and 24 h after CSEA, and adverse effects were also noted.

Results

The ED50 was 0.350 mg (95% CI, 0.259–0.376 mg) in hydromorphone group and 1.129 mg (95% CI, 0.903–1.187 mg) in morphine group, respectively, estimated by isotonic regression method. Regression analysis with the probit, the ED50 of epidural hydromorphone was 0.366 mg (95% CI, 0.276–0.388 mg) and epidural morphine was 1.138 mg (95% CI, 0.910–1.201 mg). Exploratory findings showed that there was no difference between the most frequent dosages of epidural hydromorphone or epidural morphine in the occurrence of nausea, vomiting and pruritus. When administered with epidural opioids at ED50 doses or higher, 97.5% (39/40) of epidural morphine patients and 97.5% (39/40) epidural hydromorphone of patients were satisfied with their analgesia.

Conclusion

Effective hemorrhoidectomy analgesia requires a 3:1 ratio of epidural morphine to epidural hydromorphone. Both drugs provide excellent patient satisfaction.
Effect of exercise on sleep quality in Parkinson’s disease: a mini review
Authors: Shafiq M. Abdullah , Singh Jyotpal , Khan Zain A. , Neary J. Patrick , Bardutz Holly A.
Published: January 2024

The growing incidence of Parkinson’s Disease (PD) is a major burden on the healthcare system. PD is caused by the degeneration of dopaminergic neurons and is known for its effects on motor function and sleep. Sleep is vital for maintaining proper homeostasis and clearing the brain of metabolic waste. Adequate time spent in each sleep stage can help maintain homeostatic function; however, patients with PD appear to exhibit sleep impairments. Although medications enhance the function of remaining dopaminergic neurons and reduce motor symptoms, their potential to improve sleep is still under question. Recently, research has shifted towards exercise protocols to help improve sleep in patients with PD. This review aims to provide an overview of how sleep is impaired in patients with PD, such as experiencing a reduction in time spent in slow-wave sleep, and how exercise can help restore normal sleep function. A PubMed search summarized the relevant research on the effects of aerobic and resistance exercise on sleep in patients with PD. Both high and low-intensity aerobic and resistance exercises, along with exercises related to balance and coordination, have been shown to improve some aspects of sleep. Neurochemically, sleeping leads to an increase in toxin clearance, including α-synuclein. Furthermore, exercise appears to enhance the concentration of brain-derived neurotrophic factors, which has preliminary evidence to suggest correlations to time spent in slow-wave sleep. More research is needed to further elucidate the physiological mechanism pertaining to sleep and exercise in patients with PD.
Transcutaneous canine breast cancer detection in Tunisia: a pilot study
Authors: Belaid Imtinene , Baya Mohamed Fedy , Ben Ayed Saif , Ben Ayed Ali , Maatoug Jihen , Zommit Nawel , Trabelsi Mohamed Anas , Ben Chida Noureddine , Khairi Hedi , Ben Fatma Leila , Chabchoub Imene , Ammar Nouha , Bourigua Rym , Hochlaf Makrem , Ezzaari Faten , Ben Ahmed Slim
Published: January 2024

Background

Breast cancer in Tunisia is often diagnosed at a late stage with long delay in time to consultation and to diagnosis.The aim of this study is to estimate the sensitivity and specificity of the transcutaneous breast cancer detection by canine olfactionin Tunisian women and to identify the potential confounding factors.

Methods

This is a diagnostic case control study that took place from October 2021 to November 2022 in the Department of Medical Oncology at the University Hospital Farhat Hached of Sousse and in the security and training dog center located in Sousse (K9 Dog Center Security & Training). A two-year-old male Belgian Malinois was trained to detect breast cancer on skin secretion samples in compresses that had been worn overnight by women on their breast and then a double-blind testing was performed. There was no contact between women and the dog. From the mentioned responses of the dog, four parameters were calculated: sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV).

Results

Two hundred women were included in this trial: 100 breast cancer (BC) patients recruited from Farhat Hached University Hospital of Sousse and 100 healthy volunteers (HV).The calculated sensitivity was 84% (95% CI 78–89%) and the calculated specificity was 81% (95% CI 75–86%). The calculated predictive values were: PPV = 83,51% (95% CI 78,37–88,65%) and NPV = 81,55% (95% CI 76.17–86.93%). In the multivariate study, only four confounding factors of test’s sensitivity were retained: age (OR = 1.210 [95% CI = 1.085–1.349]; p = 0.001), history of diabetes(OR = 0.017 [95% CI = 0.001–0.228]; p = 0.002), sampling at hospital (OR = 0.010 [95% CI = 0.003–0.464]; p = 0.010) and testing during chemotherapy courses (OR = 0.034 [95% CI = 0.003–0.404]; p = 0.007).For test’s specificity, we retained the three following confounding factors: age (OR = 1,104 [95% CI = 1.021–1.195]; p = 0.014), history of benign mastopathy (OR = 0.243 [95% CI = 0.074–0.805]; p = 0.021)and history of arterial hypertension (OR = 0.194 [95% CI = 0.053–0.707]; p = 0.013).

Conclusion

This is a pilot study that opens new avenues in developing a reliable cancer diagnostic tool that integrates the dog's olfactory ability to detect breast cancer using a transcutaneous sampling method. It could be a pre-test to select patients who are eligible to a screening mammogram, especially in low-income countries where there is no national mammography screening program.

Pactr.org identifier

PACTR202201864472288, registration date 11/01/2022.
Dietary Inflammatory Index and diabetic retinopathy risk in US adults: findings from NHANES (2005–2008)
Authors: Liu Rong , Zhang Jiechang , Gu Wen , Zhao Xiujuan , Xiao Lishun , Yang Chengcheng
Published: January 2024

Background

Inflammation is associated with the pathophysiology of diabetic retinopathy (DR). Within the framework of complete dietary patterns, the Dietary Inflammatory Index (DII) was formulated to evaluate the inflammatory properties inherent in a diet. The main purpose of the current study was to assess the relationship between DII and DR using National Health and Nutrition Examination Survey (NHANES).

Methods

The original sample size included 1,148 diabetes patients out of 2005–2008 NHANES surveys. Twenty-four-hour dietary consumptions were used to calculate the DII scores. Demographic characteristics and retina examinations were collected for the comparison between DR and non-DR groups in diabetes patients. The relationship between DII and DR was analyzed by a logistic regression model.

Results

227 subjects (110 non-DR and 117 DR) were selected in the analyses by using undersampling method to balance the sample size. Compared with non-DR group, DR group had higher DII values (1.14 ± 0.29 vs. 1.49 ± 0.21, p = 0.32), higher levels of HbA1c (6.8 ± 1.1% vs. 7.7 ± 2.6%, p < 0.001), longer duration of diabetes (6.52 ± 12 years vs. 14 ± 11 years, p < 0.001). The odds rate (OR) of DII for DR from the logistic regression was 1.38 (95%CI 1.06–1.81, p < 0.001). HbA1c, diabetes duration and obesity were important influencing factors, and their ORs were 1.81 (95% CI:1.31–2.50), 1.12 (95%CI:1.04–1.20), 4.01 (95%CI:1.12–14.32), respectively. In addition, the most important dietary indices for DR were different across males and females.

Conclusions

The current study demonstrates that a higher DII is associated with an increased risk of DR in US adults. Considering diet as a modifiable factor, limiting pro-inflammatory diets or encouraging an anti-inflammatory diet may be a promising and cost-effective method in the management of DR.
Source of SARS-CoV-2 infection: results from a series of 584,846 cases in France from October 2020 to August 2022
Authors: Rakover Arthur , Galmiche Simon , Charmet Tiffany , Chény Olivia , Omar Faïza , David Christophe , Martin Sophie , Mailles Alexandra , Fontanet Arnaud
Published: January 2024

Background

We aimed to study the source of infection for recently SARS-CoV-2-infected individuals from October 2020 to August 2022 in France.

Methods

Participants from the nationwide ComCor case–control study who reported recent SARS-CoV-2 infection were asked to document the source and circumstances of their infection through an online questionnaire. Multivariable logistic regression was used to identify the factors associated with not identifying any source of infection.

Results

Among 584,846 adults with a recent SARS-CoV-2 infection in France, 46.9% identified the source of infection and an additional 22.6% suspected an event during which they might have become infected. Known and suspected sources of infection were household members (30.8%), extended family (15.6%), work colleagues (15.0%), friends (11.0%), and possibly multiple/other sources (27.6%). When the source of infection was known, was not a household member, and involved a unique contact (n = 69,788), characteristics associated with transmission events were indoors settings (91.6%), prolonged (> 15 min) encounters (50.5%), symptomatic source case (64.9%), and neither the source of infection nor the participant wearing a mask (82.2%). Male gender, older age, lower education, living alone, using public transportation, attending places of public recreation (bars, restaurants, nightclubs), public gatherings, and cultural events, and practicing indoor sports were all independently associated with not knowing the source of infection.

Conclusion

Two-thirds of infections were attributed to interactions with close relatives, friends, or work colleagues. Extra-household indoor encounters without masks were commonly reported and represented avoidable circumstances of infection.

Trial registration

ClinicalTrials.gov registration number: NCT04607941.
Berberine alleviates ischemia reperfusion injury induced AKI by regulation of intestinal microbiota and reducing intestinal inflammation
Authors: Huo Aijing , Wang Fengmei
Published: January 2024

Background

It has been found that a variety of host disease states can exacerbate intestinal inflammation, leading to disruption of intestinal barrier function. Changes in the composition of the intestine microbiota, which affect downstream metabolites in turn, ultimately react against the host.

Objectives

We revealed the mechanism of berberine as an intestinal protective agent in rats with renal ischemia–reperfusion injury acute kidney injury (AKI).

Methods

HE staining was performed to evaluate the pathological changes in the colon and kidney. 16 S rRNA analysis was performed to assess the intestinal microbiota. Intestine TLR4/NF-κB expression was assessed by western blot. Q-RT-PCR was performed to detect TLR4 in intestine and IL-6 and KIM-1 gene expression in the kidney. SPSS 22.0 was used to compare the data.

Results

Rats with AKI exhibited increased relative abundances of Proteobacteria and Bacteroidetes and decreased relative abundances of Lactobacillus, Ruminococcus and Lachnospiraceae belonging to the phylum Firmicutes. The Sirt1-NF-κB-TLR4 pathway was involved in the occurrence process, accompanied by intestinal inflammation and oxidation. Berberine reversed the appeal change.

Conclusion

Berberine inhibits the intestinal biological barrier of Proteobacteria, reduces LPS production, exerts an anti-inflammatory effect, and delays the progression of AKI.
Gender trends in Canadian medicine and surgery: the past 30 years
Authors: Pickel Lauren , Sivachandran Nirojini
Published: January 2024

Background

While the number of women entering medicine has steadily increased since the 1970s in Canada, the gender composition along each stage of the medical training pathway has not been comprehensively reported. We therefore sought to systematically examine the gender composition of students, residents, and practicing physicians over the past 30 years in Canada.

Results

In this cross-sectional analysis of Canadian medical trainees including MD applicants (137,096 male, 169,099 female), MD students (126,422 male, 152, 967 female), MD graduates (29,413 male, 34,173 female), residents by the decade (24,425 male, 28,506 female) and practicing surgeons (total 7,457 male, 3,457 female), we find that increased female representation in medicine is not matched by representation in surgery, with the key being the specialty choice process. The likelihood of female applicants matriculating to medical school was less than male applicants in the 90s (OR 0.92, 95% CI 0.92–0.93), greater in the early 2000s (OR 1.03, 95% CI 1.03–1.04), and has since balanced out (OR 1.00, 95% CI 1.00-1.01), with medical school classes being nearly 60% female for the past two decades. Despite this, females have remained underrepresented in most surgical residency programs, with odds of female medical students entering surgical residency other than Ob/Gyn being about half that of male students (OR 0.56, 95% CI 0.44–0.71), resulting in a slow increase in practicing female surgeons of less than 0.5% per year in many surgical disciplines and projected parity decades or centuries in the future.

Conclusions

While undergraduate medical education has been majority female in Canada for nearly three decades, females remain greatly underrepresented in the physician workforce within surgical specialties. To build a representative medical workforce equipped to care for diverse patient populations, factors influencing the specialty choices of early career physicians will need to be examined and addressed.
Application of machine learning models on predicting the length of hospital stay in fragility fracture patients
Authors: Lai Chun-Hei , Mok Prudence Kwan-Lam , Chau Wai-Wang , Law Sheung-Wai
Published: January 2024

Background

The rate of geriatric hip fracture in Hong Kong is increasing steadily and associated mortality in fragility fracture is high. Moreover, fragility fracture patients increase the pressure on hospital bed demand. Hence, this study aims to develop a predictive model on the length of hospital stay (LOS) of geriatric fragility fracture patients using machine learning (ML) techniques.

Methods

In this study, we use the basic information, such as gender, age, residence type, etc., and medical parameters of patients, such as the modified functional ambulation classification score (MFAC), elderly mobility scale (EMS), modified Barthel index (MBI) etc, to predict whether the length of stay would exceed 21 days or not.

Results

Our results are promising despite the relatively small sample size of 8000 data. We develop various models with three approaches, namely (1) regularizing gradient boosting frameworks, (2) custom-built artificial neural network and (3) Google’s Wide & Deep Learning technique. Our best results resulted from our Wide & Deep model with an accuracy of 0.79, with a precision of 0.73, with an area under the receiver operating characteristic curve (AUC-ROC) of 0.84. Feature importance analysis indicates (1) the type of hospital the patient is admitted to, (2) the mental state of the patient and (3) the length of stay at the acute hospital all have a relatively strong impact on the length of stay at palliative care.

Conclusions

Applying ML techniques to improve the quality and efficiency in the healthcare sector is becoming popular in Hong Kong and around the globe, but there has not yet been research related to fragility fracture. The integration of machine learning may be useful for health-care professionals to better identify fragility fracture patients at risk of prolonged hospital stays. These findings underline the usefulness of machine learning techniques in optimizing resource allocation by identifying high risk individuals and providing appropriate management to improve treatment outcome.
“Whatever journey you want to take, I’ll support you through”: a mixed methods evaluation of a peer worker program in the hospital emergency department
Authors: O’Neill Meghan , Michalski Camilla , Hayman Kate , Hulme Jennifer ,   The Neighbourhood Group Community Services(Lorie Steer), Leston Florencia , Kellen Amber , Steer Lorie , Dube Sané , Diemert Lori M. , Kornas Kathy , Schoffel Alice , Rosella Laura C. , Boozary Andrew
Published: January 2024

Background

People who are unhoused, use substances (drugs and/or alcohol), and who have mental health conditions experience barriers to care access and are frequently confronted with discrimination and stigma in health care settings. The role of Peer Workers in addressing these gaps in a hospital-based context is not well characterized. The aim of this evaluation was to 1) outline the role of Peer Workers in the care of a marginalized populations in the emergency department; 2) characterize the impact of Peer Workers on patient care, and 3) to describe how being employed as a Peer Worker impacts the Peer.

Methods

Through a concurrent mixed methods evaluation, we explore the role of Peer Workers in the care of marginalized populations in the emergency department at two urban hospitals in Toronto, Ontario Canada. We describe the demographic characteristics of patients (n = 555) and the type of supports provided to patients collected through a survey between February and June 2022. Semi-structured, in-depth interviews were completed with Peer Workers (n = 7). Interviews were thematically analyzed using a deductive approach, complemented by an inductive approach to allow new themes to emerge from the data.

Results

Support provided to patients primarily consisted of friendly conversations (91.4%), discharge planning (59.6%), tactics to help the patient navigate their emotions/mental wellbeing (57.8%) and sharing their lived experience (50.1%). In over one third (38.9%) of all patient interactions, Peer Workers shared new information about the patient with the health care team (e.g., obtaining patient identification). Five major themes emerged from our interviews with Peer Workers which include: (1) Establishing empathy and building trust between the patient and their care team through self-disclosure; (2) Facilitating a person-centered approach to patient care through trauma-informed listening and accessible language; (3) Support for patient preferences on harm reduction; (4) Peer worker role facilitating self-acceptance and self-defined recovery; and (5) Importance of supports and resources to help Peer Workers navigate the emotional intensity of the emergency department.

Conclusions

The findings add to the literature on Peer Worker programs and how such interventions are designed to best meet the needs of marginalized populations.
The financial impact on people with coeliac disease of withdrawing gluten-free food from prescriptions in England: findings from a cross-sectional survey
Authors: Sugavanam Thavapriya , Crocker Helen , Violato Mara , Peters Michele
Published: January 2024

Background

A lifelong gluten-free diet is the only treatment for coeliac disease. The cost and availability of gluten-free substitute food (GFSF) remain challenging. Some local areas in England have stopped gluten-free prescriptions for coeliac disease. The aim of this paper is to present the quantitative findings of the financial impact of prescription withdrawal on people with coeliac disease.

Methods

A cross-sectional survey with adults in England who reported having been diagnosed with coeliac disease by a health professional. The postal survey was distributed by Coeliac UK to their members in 13 prescribing and 13 non-prescribing local areas that were matched for geographical location and level of deprivation. Additionally, an advertisement for the survey was placed on social media. The questionnaire contained items on the availability and use of prescriptions; the weekly amount spent on GFSF; amount of specific GFSF bought; affordability of GFSF; demographics and health-related variables. Data were analysed by descriptive statistics, analysis of variance and regression analysis.

Results

Of the 1697 participants, 809 resided in areas that provided prescriptions and 888 in non-prescribing areas. Participants self-report of their prescription did not always match the local area prescription policy. There was no statistically significant difference between prescribing and non-prescribing areas in how easy or difficult participants found it to obtain GFSF (p = 0.644) and its availability in various locations. Participants in non-prescribing areas purchased most types of GFSF items in statistically significantly higher quantities and thereby spent an additional £11.32/month on GFSF items than participants in prescribing areas (p < 0.001). While taking into account the self-reported prescription status, the amount increased to £14.09/month (p < 0.001). Although affordability to buy GFSF did not differ based on local area prescription policy or self-reported prescription status, it was dependent on equivalised annual income. However, affordability did not influence spending on GFSF. Regression analysis indicated that males and households with additional members with coeliac disease spent more on GFSF.

Conclusions

The study has highlighted that gluten-free prescription withdrawal can have financial implications for people with coeliac disease. Any future changes to the prescription policy of GFSF should consider the impact on the population, especially lower income households.
Impact of preconception and antenatal supplementation with myo-inositol, probiotics, and micronutrients on offspring BMI and weight gain over the first 2 years
Authors: Lyons-Reid Jaz , Derraik José G. B. , Kenealy Timothy , Albert Benjamin B. , Ramos Nieves J. Manuel , Monnard Cathriona R. , Titcombe Phil , Nield Heidi , Barton Sheila J. , El-Heis Sarah , Tham Elizabeth , Godfrey Keith M. , Chan Shiao-Yng , Cutfield Wayne S. ,   NiPPeR Study Group, Carvalho Ryan , Castro Julie Ann , Cavanagh Mary , Chang Hsin Fang , Chong Yap Seng , Costello Paula , Cox Vanessa , Galani Sevasti , Hammond Judith , Harvey Nicholas C. , Han Soo Min , Jagtap Mrunalini , Nembrini Chiara , O’Sullivan Justin M. , Ong Judith , Silva-Zolezzi Irma , Sim Wendy , Tay Vicky , Tint Mya-Thway , Vickers Mark , Wong Jui-Tsung , Woon Gladys , Yuan Wen Lun
Published: January 2024

Background

Nutritional intervention preconception and throughout pregnancy has been proposed as an approach to promoting healthy postnatal weight gain in the offspring but few randomised trials have examined this.

Methods

Measurements of weight and length were obtained at multiple time points from birth to 2 years among 576 offspring of women randomised to receive preconception and antenatally either a supplement containing myo-inositol, probiotics, and additional micronutrients (intervention) or a standard micronutrient supplement (control). We examined the influence on age- and sex-standardised BMI at 2 years (WHO standards, adjusting for study site, sex, maternal parity, smoking and pre-pregnancy BMI, and gestational age), together with the change in weight, length, BMI from birth, and weight gain trajectories using latent class growth analysis.

Results

At 2 years, there was a trend towards lower mean BMI among intervention offspring (adjusted mean difference [aMD] − 0.14 SD [95% CI 0.30, 0.02], p = 0.09), and fewer had a BMI > 95th percentile (i.e. > 1.65 SD, 9.2% vs 18.0%, adjusted risk ratio [aRR] 0.51 [95% CI 0.31, 0.82], p = 0.006). Longitudinal data revealed that intervention offspring had a 24% reduced risk of experiencing rapid weight gain > 0.67 SD in the first year of life (21.9% vs 31.1%, aRR 0.76 [95% CI 0.58, 1.00], p = 0.047). The risk was likewise decreased for sustained weight gain > 1.34 SD in the first 2 years of life (7.7% vs 17.1%, aRR 0.55 [95% CI 0.34, 0.88], p = 0.014). From five weight gain trajectories identified, there were more intervention offspring in the “normal” weight gain trajectory characterised by stable weight SDS around 0 SD from birth to 2 years (38.8% vs 30.1%, RR 1.29 [95% CI 1.03, 1.62], p = 0.029).

Conclusions

Supplementation with myo-inositol, probiotics, and additional micronutrients preconception and in pregnancy reduced the incidence of rapid weight gain and obesity at 2 years among offspring. Previous reports suggest these effects will likely translate to health benefits, but longer-term follow-up is needed to evaluate this.

Trial registration

ClinicalTrials.gov, NCT02509988 (Universal Trial Number U1111-1171–8056). Registered on 16 July 2015.
Isolating the effect of confounding from the observed survival benefit of screening participants — a methodological approach illustrated by data from the German mammography screening programme
Authors: Buschmann Laura , Wellmann Ina , Bonberg Nadine , Wellmann Jürgen , Hense Hans-Werner , Karch André , Minnerup Heike
Published: January 2024

Background

Mammography screening programmes (MSP) aim to reduce breast cancer mortality by shifting diagnoses to earlier stages. However, it is difficult to evaluate the effectiveness of current MSP because analyses can only rely on observational data, comparing women who participate in screening with women who do not. These comparisons are subject to several biases: one of the most important is self-selection into the MSP, which introduces confounding and is difficult to control for. Here, we propose an approach to quantify confounding based on breast cancer survival analyses using readily available routine data sources.

Methods

Using data from the Cancer Registry of North Rhine-Westphalia, Germany, we estimate the relative contribution of confounding to the observed survival benefit of participants of the German MSP. This is accomplished by comparing non-participants, participants with screen-detected and participants with interval breast cancers for the endpoints “death from breast cancer” and “death from all causes other than breast cancer” — the latter being assumed to be unrelated to any MSP effect. By using different contrasts, we eliminate the effects of stage shift, lead and length time bias. The association of breast cancer detection mode with survival is analysed using Cox models in 68,230 women, aged 50–69 years, with breast cancer diagnosed in 2006–2014 and followed up until 2018.

Results

The hazard of dying from breast cancer was lower in participants with screen-detected cancer than in non-participants (HR = 0.21, 95% CI: 0.20–0.22), but biased by lead and length time bias, and confounding. When comparing participants with interval cancers and non-participants, the survival advantage was considerably smaller (HR = 0.62, 95% CI: 0.58–0.66), due to the elimination of stage shift and lead time bias. Finally, considering only mortality from causes other than breast cancer in the latter comparison, length time bias was minimised, but a survival advantage was still present (HR = 0.63, 95% CI: 0.56–0.70), which we attribute to confounding.

Conclusions

This study shows that, in addition to stage shift, lead and length time bias, confounding is an essential component when comparing the survival of MSP participants and non-participants. We further show that the confounding effect can be quantified without explicit knowledge of potential confounders by using a negative control outcome.
Olfactory and cognitive decrements in 1991 Gulf War veterans with gulf war illness/chronic multisymptom illness
Authors: Chao Linda L.
Published: January 2024

Background

Gulf War illness (GWI)/Chronic Multisymptom Illness (CMI) is a disorder related to military service in the 1991 Gulf War (GW). Prominent symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. Although anosmia is not a typical GWI/CMI symptom, anecdotally some GW veterans have reported losing their sense smell shortly after the war. Because olfactory deficit is a prodromal symptom of neurodegenerative diseases like Parkinson’s and Alzheimer’s disease, and because we previously reported suggestive evidence that deployed GW veterans may be at increased risk for Mild Cognitive Impairment (MCI) and dementia, the current study examined the relationship between olfactory and cognitive function in deployed GW veterans.

Methods

Eighty deployed GW veterans (mean age: 59.9  ±7.0; 4 female) were tested remotely with the University of Pennsylvania Smell Identification Test (UPSIT) and the Montreal Cognitive Assessment (MoCA). Veterans also completed self-report questionnaires about their health and deployment-related exposures and experiences. UPSIT and MoCA data from healthy control (HC) participants from the Parkinson’s Progression Markers Initiative (PPMI) study were downloaded for comparison.

Results

GW veterans had a mean UPSIT score of 27.8  ± 6.3 (range 9–37) and a mean MoCA score of 25.3  ± 2.8 (range 19–30). According to age- and sex-specific normative data, 31% of GW veterans (vs. 8% PPMI HCs) had UPSIT scores below the 10th percentile. Nearly half (45%) of GW veterans (vs. 8% PPMI HCs) had MoCA scores below the cut-off for identifying MCI. Among GW veterans, but not PPMI HCs, there was a positive correlation between UPSIT and MoCA scores (Spearman’s ρ = 0.39, p < 0.001). There were no significant differences in UPSIT or MoCA scores between GW veterans with and without history of COVID or between those with and without Kansas GWI exclusionary conditions.

Conclusions

We found evidence of olfactory and cognitive deficits and a significant correlation between UPSIT and MoCA scores in a cohort of 80 deployed GW veterans, 99% of whom had CMI. Because impaired olfactory function has been associated with increased risk for MCI and dementia, it may be prudent to screen aging, deployed GW veterans with smell identification tests so that hypo- and anosmic veterans can be followed longitudinally and offered targeted neuroprotective therapies as they become available.
IL13Rα2 as a crucial receptor for Chi3l1 in osteoclast differentiation and bone resorption through the MAPK/AKT pathway
Authors: Xu Weifeng , Chao Rui , Xie Xinru , Mao Yi , Chen Xinwei , Chen Xuzhuo , Zhang Shanyong
Published: January 2024

Background

Previous research has revealed that the 18 glycoside hydrolase gene family (GH18) member Chitinase 3-like 1 (Chi3l1) can regulate osteoclast differentiation and bone resorption. However, its downstream receptors and molecular mechanisms during osteoclastogenesis have yet to be elucidated.

Methods

Initially, we conducted a comprehensive investigation to evaluate the effects of recombinant Chi3l1 protein or Chi3l1 siRNA on osteoclast differentiation and the RANKL-induced MAPK/AKT signaling pathways. Moreover, we used immunofluorescence and immunoprecipitation assays to identify IL13Rα2 as the downstream receptor of Chi3l1. Subsequently, we investigated the impact of IL13Rα2 recombinant protein or IL13Rα2-siRNA on osteoclast differentiation and the associated signaling pathways. Finally, we performed in vivo experiments to examine the effect of recombinant IL13Rα2 protein in an LPS-induced mouse model of cranial osteolysis.

Results

Our findings highlight that the administration of recombinant Chi3l1 protein increased the formation of osteoclasts and bolstered the expression of several osteoclast-specific genes (TRAP, NFATC1, CTR, CTSK, V-ATPase d2, and Dc-STAMP). Additionally, Chi3l1 significantly promoted the RANKL-induced MAPK (ERK/P38/JNK) and AKT pathway activation, whereas Chi3l1 silencing inhibited this process. Next, using immunofluorescence and co-immunoprecipitation assays, we identified IL13Rα2 as the binding partner of Chi3l1 during osteoclastogenesis. IL13Rα2 recombinant protein or IL13Rα2-siRNA also inhibited osteoclast differentiation, and IL13Rα2-siRNA attenuated the RANKL-induced activation of the MAPK (ERK/P38/JNK) and AKT pathways, similar to the effects observed upon silencing of Chi3l1. Moreover, the promoting effect of recombinant Chi3l1 protein on osteoclastogenesis and the activation of the MAPK and AKT pathways was reversed by IL13Rα2 siRNA. Finally, recombinant LI13Rα2 protein significantly attenuated the LPS-induced cranial osteolysis and the number of osteoclasts in vivo.

Conclusions

Our findings suggested that IL13Rα2 served as a crucial receptor for Chi3l1, enhancing RANKL-induced MAPK and AKT activation to promote osteoclast differentiation. These findings provide valuable insights into the molecular mechanisms of Chi3l1 in osteoclastogenesis, with potential therapeutic implications for osteoclast-related diseases.
Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis
Authors: Zhang Yi , Huang Yuchen , Qin Yanzi , Yang Ningning , Yang Panpan , Li Nan , Feng Zhenzhong
Published: January 2024

Objective

This study aimed to investigate the clinicopathological features and prognostic indicators of alveolar soft part sarcoma (ASPS).

Methods

The characteristics of 26 ASPS patients diagnosed at our hospital between January 2011 and January 2019 were retrospectively analysed.

Results

The data for 12 male and 14 female patients, with a median age of 27.5 years, were assessed. The clinical symptoms mainly included painless enlarged masses in deep soft tissues. ASPS had a characteristic pathological morphology. Twenty-four patients were positive for TFE3, and TFE3 gene rearrangement was detected in 12 patients. Among the 26 patients who completed follow-up, 14 had metastasis, 1 had local recurrence, and 7 died. Kaplan–Meier survival analysis revealed that prognosis was significantly correlated with sex, tumour size and metastasis (P < 0.05). Multivariate Cox regression analysis revealed that sex and metastasis were independent prognostic risk factors for patients with ASPS (P < 0.05).

Conclusion

ASPS is a rare soft tissue sarcoma of unknown origin that occurs in young people, has a slow but metastatic course, and is associated with a poor 5-year survival rate among patients with metastasis. ASPS has character TFE3 protein and gene expression, and the diagnosis is relatively specific. The diagnosis requires comprehensive analysis of clinical history, histological morphology, and immunohistochemistry.
Universal health coverage in the context of population ageing: catastrophic health expenditure and unmet need for healthcare
Authors: Okamoto Shohei , Sata Mizuki , Rosenberg Megumi , Nakagoshi Natsuko , Kamimura Kazuki , Komamura Kohei , Kobayashi Erika , Sano Junko , Hirazawa Yuzuki , Okamura Tomonori , Iso Hiroyasu
Published: January 2024

Background

Universal health coverage means that all people can access essential health services without incurring financial hardship. Even in countries with good service coverage and financial protection, the progress towards universal health coverage may decelerate or be limited with respect to the growing older population. This study investigates the incidence/prevalence, determinants, and consequences of catastrophic health expenditure (CHE) and unmet need for healthcare and assesses the potential heterogeneity between younger (≤ 64 years) and older people (65 years≤).

Methods

Utilising an annual nationally representative survey of Japanese aged 20 years and over, we estimated the incidence of CHE and unmet need for healthcare using disaggregated estimates by household members’ age (i.e. ≤64 years vs. 65 years≤) between 2004 and 2020. Using a fixed-effects model, we assessed the determinants of CHE and unmet need along with the consequences of CHE. We also assessed the heterogeneity by age.

Results

Households with older members were more likely to have their healthcare needs met but experienced CHE more so than households without older members. The financial consequences of CHE were heterogeneous by age, suggesting that households with older members responded to CHE by reducing food and social expenditures more so than households without older members reducing expenditure on education. Households without older members experienced an income decline in the year following the occurrence of CHE, while this was not found among households with older members. A U-shaped relationship was observed between age and the probability of experiencing unmet healthcare need.

Conclusions

Households with older members are more likely to experience CHE with different financial consequences compared to those with younger members. Unmet need for healthcare is more common among younger and older members than among their middle-aged counterparts. Different types and levels of health and financial support need to be incorporated into national health systems and social protection policies to meet the unique needs of individuals and households.
Children’s active school transportation: an international scoping review of psychosocial factors
Authors: Savolainen Eva , Lindqvist Anna-Karin , Mikaelsson Katarina , Nyberg Lars , Rutberg Stina
Published: January 2024

Background

Over the last decades, the prevalence of AST has decreased significantly. Barriers to active school transport (AST) have been extensively examined in the literature, while psychosocial factors that facilitate AST have received less attention. To our best knowledge, there are currently no reviews on this subject. Therefore, the objective of this review was to scope the literature and identify published research about psychosocial factors related to AST.

Methods

Systematic searches conducted in PubMed, Web of Science, TRID, Scopus, and ERIC resulted in a total of 1933 publications, and 77 of them were considered eligible for this review.

Results

The results of the included articles were categorised into four psychosocial factors: confidence in ability, attitudes, social support, and social norms, which were all generally positively related to AST, with a few exceptions.

Conclusion

The findings of this review indicate that these psychosocial factors may be important to consider when developing interventions and highlight that both children and parents should be involved in the process. This knowledge can serve as a valuable guide for developing interventions to promote AST. However, the evidence base supporting these psychosocial factors requires further investigation to fully understand how and when to incorporate them to maximise AST efficacy.
Factors influencing long-term outcomes in fibrotic interstitial lung disease (F-ILD) diagnosed through multidisciplinary discussion (MDD): a prospective cohort study
Authors: Liao Yu-Wan , Liu Ming-Cheng , Wu Yu-Cheng , Hsu Chiann-Yi , Huang Wen-Nan , Chen Yi-Hsing , Fu Pin-Kuei
Published: January 2024

Background

The diagnostic process for fibrotic interstitial lung disease (F-ILD) is notably intricate, necessitating a multidisciplinary discussion to achieve consensus based on both clinical and radiological features. This study investigated the shared and distinctive long-term mortality predictors among the two primary phenotypes of F-ILD, namely idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD).

Methods

We included patients with F-ILD diagnosed from December 2018 to December 2019 and conducted follow-up assessments until February 2023. Age, gender, usual interstitial pneumonia (UIP) pattern, gender–age–physiology (GAP) score, modified Medical Research Council (mMRC) dyspnea score, antifibrotic agent use, pulmonary function test parameters, and six-minute walking test (6MWT) parameters were recorded at baseline and used as mortality predictors in a multivariate Cox regression model.

Results

We enrolled 104 ILD patients. The survival rate of non-IPF patients was more than twice that of IPF patients (78.9% vs. 34%, p < 0.001), and the survival rate of patients with a GAP score of 0–2 was more than twice that of patients with a score of > 2 (93.2% vs. 36.6%, p < 0.001). Older age, male gender, definite UIP pattern, higher GAP score, higher mMRC dyspnea score, lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC), shorter 6MWT distance, and lower initial and final SpO2 were also associated with higher long-term mortality (p < 0.05). In multivariable analysis, only a GAP score of > 2 (hazard ratio [HR]:16.7; 95% confidence interval [CI] 3.28–85.14; p = 0.001) and definite UIP pattern (HR: 4.08; 95% CI 1.07–15.5; p = 0.039) were significantly associated with overall mortality.

Conclusion

The long-term mortality rate of IPF patients was higher than that of CTD-ILD patients. The GAP score and UIP patterns were significant mortality predictors for both IPF and CTD-ILD patients.
Experimental seismic crosshole setup to investigate the application of rock-physical models at the field scale
Authors: Birnstengel Susann , Dietrich Peter , Peisker Kilian , Pohle Marco , Hornbruch Götz , Bauer Sebastian , Hu Linwei , Günther Thomas , Hellwig Olaf , Dahmke Andreas , Werban Ulrike
Published: January 2024

Seismic crosshole techniques are powerful tools to characterize the properties of near-surface aquifers. Knowledge of rock-physical relations at the field scale is essential for interpreting geophysical measurements. However, it remains difficult to extend the results of existing laboratory studies to the field scale due to the usage of different frequency ranges. To address this, we develop an experimental layout that successfully determines the dependency of gas saturation on seismic properties. Integrating geophysical measurements into a hydrogeologic research question allows us to prove the applicability of theoretical rock-physical concepts at the field scale, filling a gap in the discipline of hydrogeophysics. We use crosshole seismics to perform a time-lapse study on a gas injection experiment at the TestUM test site. With a controlled two-day gaseous [Formula: see text] injection at a depth of 17.5 m, we monitor the alteration of water saturation in the sediments over a period of 12 months, encompassing an observational depth of 8–13 m. The investigation contains an initial P-wave simulation followed by a data-based P-wave velocity analysis. Subsequently, we discuss different approaches to quantifying gas content changes by comparing Gassmann’s equation and the time-average relation. With the idea of patchy saturation, we discover that analyzing P-wave velocities in the subsurface is a suitable method for our experiment, resulting in a measurement accuracy of 0.2 vol%. We determine that our seismic crosshole setup is able to describe the relation of the rock’s elastic parameter on modified fluid properties at the field scale. With this method, we are able to quantify the relative water content changes in the subsurface.
Q-compensated image-domain least-squares reverse time migration through preconditioned point-spread functions
Authors: Zhang Wei , Gao Jinghuai , Shi Ying , Ke Xuan , Li Zhen , Yang Tao , Sun Wenbo
Published: January 2024

Image-domain least-squares reverse time migration (IDLSRTM) through point-spread functions (PSFs) has been proven to be a feasible approach to improve the spatial resolution and amplitude fidelity of reflection images recovered by reverse time migration (RTM). However, it usually ignores the earth’s Q-effects, which may lead to an unfocused reflection image with an undesired spatial resolution. In this paper, we develop a Q-compensated IDLSRTM approach (denoted as Q-IDLSRTM) through PSFs, in which we use the viscoacoustic wave equation based on the generalized standard linear solid model to simulate inherent subsurface attenuation and the linear inversion to compensate for the amplitude attenuation. The PSFs are estimated by a round of modeling-migration computation and spatial interpolation on the fly. There are two key points in the developed Q-IDLSRTM approach. The first is that we must apply the deblurring filter as a preconditioner to compensate for the attenuation of image amplitude of PSFs and RTM in a viscoacoustic medium, before the iterative solution. The preconditioned PSFs and RTM images can help us to construct a less ill-posed image-domain inverse problem that can produce an improved image quality and a faster convergence rate, compared with the conventional Q-IDLSRTM approach without the deblurring filter. The second key point is that we can impose the L1-norm constraint and total variation regularization on the reflection image to stabilize the solution of the ill-posed inverse problem. Several 2D and 3D experiments verify that the developed approach can achieve better imaging quality in terms of amplitude fidelity and spatial resolution relative to the conventional Q-IDLSRTM and acoustic IDLSRTM approaches.
The Clinical Impact of Sample Storage at −20 °C on Renin Reference Intervals and Aldosterone–Renin Ratio Calculations
Authors: Özcan Ömer , Hillebrand Jacquelien J , den Elzen Wendy , Heijboer Annemieke C
Published: January 2024

Cryoactivation is known to occur in whole blood and plasma samples when kept between +4 and −5 °C, leading to falsely high renin concentrations. In 2022 it has been clearly shown that cryoactivation can also occur in samples stored at −20 °C. Based on these new findings, here we discuss how this can influence the clinical diagnosis of patients. First, we show that storage of renin plasma samples can affect the renin measurements and thereby the aldosterone to renin ratio (ARR) calculation, which might explain the high intraindividual variability in ARR also recently demonstrated. Second, we discuss the existing studies on the establishment of renin reference intervals and note the lack of attention given to this recently revealed preanalytical condition. Our literature review of the reference intervals for renin suggest that cryoactivation might have influenced the published data.