bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of dexmedetomidine administration on analgesic, respiration and inflammatory responses in patients undergoing percutaneous endoscopic lumbar discectomy: a prospective observational study
Authors: Zhang Xiaoli , Zhao Wenping , Sun Cong , Huang Zhihua , Zhan Lifang , Xiao Chunlin , Lai Luying , Shan Reai
Published: May 2022

Background

Local anesthesia has been recommended for percutaneous endoscopic lumbar discectomy (PELD) in recent years; however, the efficacy, including oxidative stress, inflammatory reactions and ventilation effects, when intravenous dexmedetomidine (DEX) is administered during PELD has not been described.

Methods

Sixty adult patients undergoing PELD were randomly allocated to either an intravenous DEX sedation group (Group A) or a normal saline group (Group B). Respiratory data, including minute ventilation (MV), tidal volume (TV), and respiratory rate (RR), were recorded using a respiratory volume monitor (RVM), and peripheral oxygen saturation (SpO2) was monitored by pulse oximetry. The visual analog score (VAS) was used to assess the level of pain. The serum levels of inflammatory biomarkers including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were to assess inflammatory reactions. The serum levels of oxidative stress biomarkers including malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) were also recorded to evaluate oxidative stress.

Results

There were no significant differences in RR, MV, TV and SpO2 between the two groups at any time point (P > 0.05). Group B exhibited lower serum levels of GSH-PX (P < 0.0001) and higher serum levels of MDA (p < 0.0001) than Group A at the end of surgery. Twenty-four hours after surgery, Group B exhibited higher serum levels of IL-6 (P = 0.0033), TNF-α (P = 0.0002), and MDA (P < 0.0001) and lower serum levels of GSH-PX (P < 0.0001) than Group A. In addition, Group A exhibited lower VAS (P < 0.0001) than Group B during surgery.

Conclusions

DEX administration using RVM not only provides analgesia without ventilatory depression but also alleviates oxidative stress and inflammatory reactions in patients undergoing PELD.
Cesarean delivery in Norwegian nulliparous women with singleton cephalic term births, 1967–2020: a population-based study
Authors: Sima Yeneabeba Tilahun , Skjærven Rolv , Kvalvik Liv Grimstvedt , Morken Nils-Halvdan , Klungsøyr Kari , Sørbye Linn Marie
Published: May 2022

Background

Nulliparous women contribute to increasing cesarean delivery in the Nordic countries and advanced maternal age has been suggested as responsible for rise in cesarean delivery rates in many developed countries. The aim was to describe changes in cesarean delivery rates among nulliparous women with singleton, cephalic, term births by change in sociodemographic factors across 50 years in Norway.

Methods

We used data from the Medical Birth Registry of Norway and included 1 067 356 women delivering their first, singleton, cephalic, term birth between 1967 and 2020. Cesarean delivery was described by maternal age (5-year groups), onset of labor (spontaneous, induced and pre-labor CD), and time periods: 1967–1982, 1983–1998 and 1999–2020. We combined women’s age, onset of labor and time period into a compound variable, using women of 20–24 years, with spontaneous labor onset during 1967–1982 as reference. Multivariable regression models were used to estimate adjusted relative risk (ARR) of cesarean delivery with 95% confidence interval (CI).

Results

Overall cesarean delivery increased both in women with and without spontaneous onset of labor, with a slight decline in recent years. The increase was mainly found among women < 35 years while it was stable or decreased in women >  = 35 years. In women with spontaneous onset of labor, the ARR of CD in women >  = 40 years decreased from 14.2 (95% CI 12.4–16.3) in 1967–82 to 6.7 (95% CI 6.2–7.4) in 1999–2020 and from 7.0 (95% CI 6.4–7.8) to 5.0 (95% CI 4.7–5.2) in women aged 35–39 years, compared to the reference population. Despite the rise in induced onset of labor over time, the ARR of CD declined in induced women >  = 40 years from 17.6 (95% CI 14.4–21.4) to 13.4 (95% CI 12.5–14.3) while it was stable in women 35–39 years.

Conclusion

Despite growing number of Norwegian women having their first birth at a higher age, the increase in cesarean delivery was found among women < 35 years, while it was stable or decreased in older women. The increase in cesarean delivery cannot be solely explained by the shift to an older population of first-time mothers.
Downregulation of angiogenic factors in aqueous humor associated with less intraoperative bleeding in PDR patients with NVG receiving conbercept: a randomized controlled trial
Authors: Xu Qing , Gong Chaoju , Qiao Lei , Feng Ruifang , Liu Haiyang , Liu Yalu , Yang Liu , Fan Wei , Guan Lina , Li Jie , Zhang Yipeng , Li Suyan
Published: May 2022

Background

To analyze the level changes of 28 cytokines in aqueous humor of patients with proliferative diabetic retinopathy (PDR) coexisting neovascular glaucoma (NVG) after intravitreal injection of conbercept (IVC), and to investigate whether these cytokines are associated with intraoperative bleeding (IOB).

Methods

Totally 34 eyes with NVG secondary to PDR were enrolled. Patients were randomized into two groups, and all of them underwent 25-gauge pars plana vitrectomy (PPV) combined with trabeculectomy. Group I, 18 eyes received IVC 3 days before PPV, and 100 µL aqueous humor was collected at the time of IVC pretreatment and 3 days later at the beginning of PPV respectively. Group II, 16 eyes received IVC after PPV, and 100 µL aqueous humor was collected only at the beginning of PPV. Aqueous humor from 19 eyes with age-matched cataract patients served as controls. Luminex bead-based multiplex array was used to measure the levels of 28 cytokines in aqueous humor. The baseline cytokine levels were compared among the three groups. All NVG patients were divided into IOB and non-bleeding (INB) groups. The cytokine levels of aqueous humor at the beginning of PPV were compared between group I and II, also between IOB and INB groups. IOB in NVG patients was graded according to vitreous bleeding amount. The correlation between cytokine levels and the grades of IOB were analyzed.

Results

Compared with controls, the baseline levels of 18 cytokines associated with inflammation and angiogenesis showed significantly increased in group I and group II (all, P < 0.0167). The IOB rate as well as the levels of IL-4, IL-22, Ang-2, PLGF and VEGF-A in group I were significantly lower than in group II (all, P < 0.05). The levels of IL-4, IL-22, Ang-2, PLGF and VEGF-A were significantly lower in INB group than in IOB group (all, P < 0.05). The levels of IL-4, Ang-2, PLGF and VEGF-A were positively correlated with the grades of IOB in NVG patients (all, rs > 0.4, P < 0.05).

Conclusions

IVC 3 days before PPV combined with trabeculectomy reduces IOB in NVG patients, in which the downregulation of IL-4, Ang-2, PLGF and VEGF-A after IVC may be an underlying mechanism.

Trial registration

ChiCTR2100048118, retrospectively registered on 2 July 2021.
Perceptions of patient aggression in psychiatric hospitals: a qualitative study using focus groups with nurses, patients, and informal caregivers
Authors: Välimäki Maritta , Lantta Tella , Lam Yuen Ting Joyce , Cheung Teris , Cheng Po Yee Ivy , Ng Tony , Ip Glendy , Bressington Daniel
Published: May 2022

Background

Aggression in psychiatric hospitals has been of interest to researchers. Information on how different stakeholders perceive patient aggression remains equivocal. Even less is known about possible similarities or differences in stakeholders’ perceptions of how aggressive behaviour is understood, managed and prevented in psychiatric hospitals. We aimed to explore multiple viewpoints on patient aggression, its possible causes and outcomes, and development ideas for prevention and management.

Methods

A qualitative design was adopted. The data were collected using focus group interviews. A thematic approach was used for interpretation. The data were collected on 15 adult wards in two inpatient psychiatric settings in Hong Kong. Participants were nurses working on the psychiatric inpatient wards, patients admitted to the wards, and informal caregivers visiting inpatient wards (N = 94).

Results

Commonalities between all groups were found on how patient aggression is perceived, and why it occurs. Patients and especially nurses described how patient aggression occurred with no clear reason or forewarning and how patients were physically controlled or restricted after aggressive events. Only nurses and patients expressed experiencing physical burden, while all groups considered psychological burden to be a consequence of aggression. All groups proposed that helpful attitudes among nurses, better communication, structural changes, and better self-management skills would prevent patient aggression. Risk assessment was proposed only by nurses and patients, while safety measures were proposed by nurses and informal caregivers only. The use of restrictive interventions to manage aggressive events was proposed by all groups.

Conclusions

Despite the complex diversity of perspectives in different stakeholder groups regarding patient aggression, the findings highlighted that it is possible to achieve some mutual understanding of aggression in psychiatric hospitals and identify areas to be developed. Staffs’ attitudes and skills for engagement and communication with patients and informal caregivers should be improved. There is also still room to develop the therapeutic environment and culture toward meaningful activities during the treatment period.
Characteristics and clinical outcomes of patients with nonsmoking small cell lung cancer in Korea
Authors: Kang Hye Seon , Lim Jung Uk , Yeo Chang Dong , Park Chan Kwon , Lee Sang Haak , Kim Seung Joon ,   Korean Association for Lung Cancer, Korea Central Cancer Registry, Kim Ho Cheol , Choi Chang Min , Jung Chi Young , Cho Deog Gon , Jeon Jae Hyun , Lee Jeong Eun , Ahn Jin Seok , Kim Yeongdae , Choi Yoo-Duk , Suh Yang-Gun , Kim Jung-Eun , Won Young-Joo , Kim Young-Chul
Published: May 2022

Background

The aim of this study was to investigate the characteristics and clinical outcomes of patients with nonsmoking small cell lung cancer (SCLC) using a nationwide registry in Korea.

Methods

The Korean Association for Lung Cancer developed a registry in cooperation with the Korean Central Cancer Registry (KCCR) and surveyed approximately 10% of recorded lung cancer cases.

Results

From 2014 to 2016, the KCCR registered 1,043 patients newly diagnosed with SCLC among a total of 8,110 lung cancer patients. In subgroup analysis, Kaplan meier survival analysis showed that the overall survival (OS) was significantly shorter in the nonsmoking subgroup than the ever-smoking subgroup of SCLC patients with extensive disease (6.99 vs. 9.68 months; P = 0.016). Among SCLC patients with limited disease, OS was also shorter in the nonsmoking subgroup, without statistical significance (19.4 vs. 23.5 months; P = 0.247). In a multivariate analysis using a Cox regression model, never smoking was not associated with shorter OS, but older age, extensive stage, poor performance status (Eastern Cooperative Oncology Group grade ≥ 2), male sex, no prophylactic cranial irradiation, and no active treatment (chemotherapy and/or radiotherapy) were associated with poor prognosis.

Conclusion

This evaluation of an unbiased nationwide survey dataset revealed that a significant proportion of Korean SCLC patients were never-smokers. No history of smoking appeared to be a significant prognostic factor according to the univariate analysis but was confirmed to be statistically insignificant through a multivariate analysis of the total population. Reasons for a poor prognosis may include the possibility that a high rate of the elderly population is composed of nonsmokers who did not receive active treatment.
Maternal and infant risk factors and risk indicators associated with early childhood caries in South Africa: a systematic review
Authors: Kimmie-Dhansay Faheema , Barrie Robert , Roberts Tina , Naidoo Sudeshni
Published: May 2022

Objectives

To evaluate the risk factors and risk indicators associated with early childhood caries in South Africa.

Design

A systematic review of aetiology was performed. From 1366 papers found, 23 studies met the eligibility criteria and were included. All study designs were included. Healthy children under six who live in South Africa were eligible for the study. The study was registered with PROSPERO, registration number CRD42020216455.

Data extraction

Eligible studies were selected, and data extracted independently by two reviewers. Published data on socio-economic status, dietary factors, oral hygiene knowledge and practices, breastfeeding and bottle-feeding practices, oral bacterial flora and other risk indicators were collected. Two authors appraised the studies independently using the Joanna Briggs Critical Appraisal tools.

Data analysis

Heterogeneity was assessed using the I2 statistics, and due to heterogeneity, extracted data were mostly presented narratively.

Results

Meta-analysis was performed using random-effects models and concluded that parents of children who had a tertiary education had a 1.77 [1.22–2.57] odds of experiencing dental caries compared to the children of parents with a secondary education. However, the unclear risk of bias of most included cross-sectional studies precluded definitive conclusions.

Conclusions

More high-quality cohort studies need to be performed to evaluate actual risk factors for ECC in a South African setting. Parental/caregiver oral educational knowledge needs promoting before the emergence of their children’s teeth. The social determinants of health need to be incorporated in future studies, and suitable targeted interventions need to be developed and implemented to mitigate early childhood caries in South Africa.
Determinants of modern contraceptive utilization among married women in sub-Saharan Africa: multilevel analysis using recent demographic and health survey
Authors: Tesema Zemenu Tadesse , Tesema Getayeneh Antehunegn , Boke Moges Muluneh , Akalu Temesgen Yihunie
Published: May 2022

Background

Family planning is a low-cost, high-impact public health and development strategy to improve child and maternal health. However, there is a lack of evidence on modern contraceptive use and determinants in sub-Saharan Africa. Hence, this study aimed at determining the pooled prevalence and determinants of modern contraceptive utilization among married women of sub-Saharan Africa.

Methods

Thirty-six sub-Saharan African countries' demographic and health survey (DHS) data were used for pooled analysis. A total weighted sample of 322,525 married women was included. Cross tabulations and summary statistics were done using STATA version 14 software. The pooled prevalence of modern contraceptive utilization with a 95% Confidence Interval (CI) was reported. Multilevel regression analysis was used to identify the determinants of modern contraceptive use among married women. Four models were fitted to select the best-fitted model using the Likelihood Ratio (LLR) and Deviance test. Finally, the model with the highest LLR and the smallest deviance was selected as the best-fitted model.

Results

The pooled estimate of modern contraception use in sub–Saharan African countries was 18.36% [95% CI: 18.24, 18.48], with highest in Lesotho (59.79%) and the lowest in Chad (5.04%). The odds of modern contraception utilization were high among women living in East Africa [AOR = 1.47 (1.40, 1.54)], urban areas [AOR = 1.18 (1.14, 1.24)], and women with primary [AOR = 1.49 (1.44, 1.55)] and secondary and above educational level [AOR = 1.66 (1.58, 1.74)]. Moreover, husbands with primary educational level [AOR = 1.38 (1.33, 1.42)], middle [AOR = 1.17, (1.14, 1.21)], rich wealth status [AOR = 1.29 (1.25, 1.34)], media exposure [AOR = 1.25 (1.22, 1.29)], and postnatal care (PNC) utilization [AOR = 1.25 (1.22, 1.29)] had higher odds of modern contraceptive utilization compared with their counter parts. Furthermore, deliver at health facility [AOR = 1.74 (1.69, 1.79)] and birth order 2–4 [AOR = 1.36 (1.31, 1.41)] had higher odds of modern contraceptive utilization. On the other hand, women living in Central [AOR = 0.23 (0.22, 0.24)], Western regions [AOR = 0.46 (0.40, 0.54)], women who decided with husband [AOR = 0.90 (0.87, 0.93)], and decisions by husband alone [AOR = 0.73 (0.71, 0.75)] decreased the odds of modern contraceptive utilization.

Conclusion

The uptake of modern contraception in sub-Saharan Africa is low. Modern contraceptive utilization is affected by different factors. More attention needs to be given to rural residents, illiterate women, and communities with low wealth status.
The effect of cancer on traditional, complementary and alternative medicine utilization in Korea: a fixed effect analysis using Korea Health Panel data
Authors: Kim Dongsu , Sung Soo-Hyun , Shin Seungwon , Park Minjung
Published: May 2022

Background

Cancer-related incidence and mortality rates are rapidly increasing worldwide. However, no studies have examined the effect of cancer as a single factor on the use of traditional, complementary, and alternative medicine (T&CAM). We aimed to determine the effect of cancer occurrence on T&CAM utilization using Korea Health Panel (KHP) data.

Methods

We analyzed longitudinal data (49,380 observations) derived from 12,975 Korean adult participants with complete KHP data from 2011 to 2014 and 2016, and divided them into two groups based on cancer diagnosis. A panel multinomial logit model was used to assess whether the participants used T&CAM or conventional medicine or both in outpatient settings. Additionally, a negative binomial regression model was used to examine the effect of cancer on the number of outpatient visits for T&CAM.

Results

In total, 25.54% of the study participants in the cancer group used T&CAM, which was higher than that in the non-cancer group (18.37%, p < 0.0001). A panel multinomial logistic regression analysis using KHP data showed that cancer occurrence was significantly more likely to be associated with ‘Using both Korean medicine and conventional medicine’ (Coef. = 0.80, p = 0.017) and ‘Not using Korean medicine but using conventional medicine’ (Coef. = 0.85, p = 0.008) than ‘Not using Korean medicine and conventional medicine.’ A panel negative binomial regression showed a significant effect of cancer on increasing the number of T&CAM outpatient visits (Coef. = 0.11, p = 0.040).

Conclusions

Our findings showed that cancer occurrence within an individual led to the simultaneous use of conventional medicine and T&CAM. In addition, the occurrence of cancer significantly increased the number of T&CAM outpatient visits among participants already using T&CAM. It was also found that T&CAM has been utilized more often by the most vulnerable people, such as medical beneficiaries and those with a low level of education.
A qualitative study of senior management perspectives on the leadership skills required in regional and rural Australian residential aged care facilities
Authors: Dawes Nathan , Topp Stephanie M.
Published: May 2022

Background

With increasing recognition of the quality and safety issues in residential aged care, there is an urgent need to better understand what skills senior managers require to deliver on the spectrum of leadership functions in residential aged care facilities. This qualitative study sought to explore the leadership skills that positively influence the quality of care within Australian residential aged care facilities and better understand the professional development needs of senior managers to positively influence care within these complex environments.

Methods

We conducted semi-structured interviews with 19 senior managers purposively recruited from 14 high-performing non-government residential aged care facilities of varying geographical remoteness in northern Queensland, Australia. Participants held a range of professional roles, including Chief Executive Officer, Director of Nursing and Facility Manager, and had various professional qualifications. We used inductive thematic analysis to identify and categorise senior managers’ perspectives on the leadership skills and related strategies to promote quality of care.

Results

Senior managers reported leadership skills in five major domains: i) communication and relationship management, ii) stewardship, iii) professional development, iv) health care knowledge and v) information technology and finance. Most participants highlighted communication and relationship management skills and responding to regulatory change as influential to residential aged care quality performance. Participants with different professional backgrounds often emphasised different skills.

Conclusions

Participants identified a broad range of skills and strategies required by senior managers in Australian residential aged care facilities. Identifying different skills by differently trained individuals suggests more work is needed to understand and develop sector-specific professional development approaches to better prepare individuals to lead in this complex service environment.
MAIT cell counts are associated with the risk of hospitalization in COPD
Authors: Pincikova Terezia , Parrot Tiphaine , Hjelte Lena , Högman Marieann , Lisspers Karin , Ställberg Björn , Janson Christer , Malinovschi Andrei , Sandberg Johan K.
Published: May 2022

Background

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation associated with chronic inflammation in the airways. Mucosal-associated invariant T (MAIT) cells are unconventional, innate-like T cells highly abundant in mucosal tissues including the lung. We hypothesized that the characteristics of MAIT cells in circulation may be prospectively associated with COPD morbidity.

Methods

COPD subjects (n = 61) from the Tools for Identifying Exacerbations (TIE) study were recruited when in stable condition. At study entry, forced expiratory volume in 1 s (FEV1) was measured and peripheral blood mononuclear cells were cryopreserved for later analysis by flow cytometry. Patients were followed for 3 years to record clinically meaningful outcomes.

Results

Patients who required hospitalization at one or more occasions during the 3-year follow-up (n = 21) had lower MAIT cell counts in peripheral blood at study inclusion, compared with patients who did not get hospitalized (p = 0.036). In contrast, hospitalized and never hospitalized patients did not differ in CD8 or CD4 T cell counts (p = 0.482 and p = 0.221, respectively). Moreover, MAIT cells in hospitalized subjects showed a more activated phenotype with higher CD38 expression (p = 0.014), and there was a trend towards higher LAG-3 expression (p = 0.052). Conventional CD4 and CD8 T cells were similar between the groups. Next we performed multi-variable logistic regression analysis with hospitalizations as dependent variable, and FEV1, GOLD 2017 group, and quantity or activation of MAIT and conventional T cells as independent variables. MAIT cell count, CD38 expression on MAIT cells, and LAG-3 expression on both MAIT and CD8 T cells were all independently associated with the risk of hospitalization.

Conclusions

These findings suggest that MAIT cells might reflect a novel, FEV1-independent immunological dimension in the complexity of COPD. The potential implication of MAIT cells in COPD pathogenesis and MAIT cells’ prognostic potential deserve further investigation.
Notch ankyrin domain: evolutionary rise of a thermodynamic sensor
Authors: Vujovic Filip , Hunter Neil , Farahani Ramin M.
Published: May 2022

Notch signalling pathway plays a key role in metazoan biology by contributing to resolution of binary decisions in the life cycle of cells during development. Outcomes such as proliferation/differentiation dichotomy are resolved by transcriptional remodelling that follows a switch from Notchon to Notchoff state, characterised by dissociation of Notch intracellular domain (NICD) from DNA-bound RBPJ. Here we provide evidence that transitioning to the Notchoff state is regulated by heat flux, a phenomenon that aligns resolution of fate dichotomies to mitochondrial activity. A combination of phylogenetic analysis and computational biochemistry was utilised to disclose structural adaptations of Notch1 ankyrin domain that enabled function as a sensor of heat flux. We then employed DNA-based micro-thermography to measure heat flux during brain development, followed by analysis in vitro of the temperature-dependent behaviour of Notch1 in mouse neural progenitor cells. The structural capacity of NICD to operate as a thermodynamic sensor in metazoans stems from characteristic enrichment of charged acidic amino acids in β-hairpins of the ankyrin domain that amplify destabilising inter-residue electrostatic interactions and render the domain thermolabile. The instability emerges upon mitochondrial activity which raises the perinuclear and nuclear temperatures to 50 °C and 39 °C, respectively, leading to destabilization of Notch1 transcriptional complex and transitioning to the Notchoff state. Notch1 functions a metazoan thermodynamic sensor that is switched on by intercellular contacts, inputs heat flux as a proxy for mitochondrial activity in the Notchon state via the ankyrin domain and is eventually switched off in a temperature-dependent manner.
Certificate-of-need laws and substance use treatment
Authors: Bailey James , Lu Thanh , Vogt Patrick
Published: May 2022

Background

Certificate-of-need (CON) laws in place in most US states require healthcare providers to prove to a state board that their proposed services are necessary in order to be allowed to open or expand. While CON laws most commonly target hospital and nursing home beds, many states require CONs for other types of healthcare providers and services. As of 2020, 23 states retain CON laws specifically for substance use treatment, requiring providers to prove their “economic necessity” before opening or expanding. In contrast to the extensive academic literature on how hospital and nursing home CON laws affect costs and access, substance use CON laws are essentially unstudied.

Methods

Using 2002–19 data on substance use treatment facilities from the Substance Abuse and Mental Health Services Administration’s National Survey of Substance Abuse Treatment Services, we measure the effect of CON laws on access to substance use treatment. Using fixed-effects analysis of states enacting and repealing substance use CON laws, we measure how CON laws affect the number of substance use treament facilities and beds per capita in a state.

Results

We find that CON laws have no statistically significant effect on the number of facilities, beds, or clients and no significant effect on the acceptance of Medicare. However, they reduce the acceptance of private insurance by a statistically significant 6.0%.

Conclusions

Policy makers may wish to reconsider whether substance use CON laws are promoting their goals.
TTCOV19: timing of tracheotomy in SARS-CoV-2-infected patients: a multicentre, single-blinded, randomized, controlled trial
Authors: Eeg-Olofsson Måns , Pauli Nina , Hafsten Louise , Jacobsson Josephine , Lundborg Christopher , Brink Magnus , Larsson Helen , Lindell Ellen , Löwhagen Karin , Gisslén Magnus , Bergquist Henrik
Published: May 2022

Background

Critically ill COVID-19 patients may develop acute respiratory distress syndrome and the need for respiratory support, including mechanical ventilation in the intensive care unit. Previous observational studies have suggested early tracheotomy to be advantageous. The aim of this parallel, multicentre, single-blinded, randomized controlled trial was to evaluate the optimal timing of tracheotomy.

Methods

SARS-CoV-2-infected patients within the Region Västra Götaland of Sweden who needed intubation and mechanical respiratory support were included and randomly assigned to early tracheotomy (≤ 7 days after intubation) or late tracheotomy (≥ 10 days after intubation). The primary objective was to compare the total number of mechanical ventilation days between the groups.

Results

One hundred fifty patients (mean age 65 years, 79% males) were included. Seventy-two patients were assigned to early tracheotomy, and 78 were assigned to late tracheotomy. One hundred two patients (68%) underwent tracheotomy of whom sixty-one underwent tracheotomy according to the protocol. The overall median number of days in mechanical ventilation was 18 (IQR 9; 28), but no significant difference was found between the two treatment regimens in the intention-to-treat analysis (between-group difference: − 1.5 days (95% CI − 5.7 to 2.8); p = 0.5). A significantly reduced number of mechanical ventilation days was found in the early tracheotomy group during the per-protocol analysis (between-group difference: − 8.0 days (95% CI − 13.8 to − 2.27); p = 0.0064). The overall correlation between the timing of tracheotomy and days of mechanical ventilation was significant (Spearman’s correlation: 0.39, p < 0.0001). The total death rate during intensive care was 32.7%, but no significant differences were found between the groups regarding survival, complications or adverse events.

Conclusions

The potential superiority of early tracheotomy when compared to late tracheotomy in critically ill patients with COVID-19 was not confirmed by the present randomized controlled trial but is a strategy that should be considered in selected cases where the need for MV for more than 14 days cannot be ruled out.

Trial registrationNCT04412356, registered 05/24/2020.

Graphic abstract
Rapid molecular diagnostics of tuberculosis resistance by targeted stool sequencing
Authors: Sibandze Doctor B. , Kay Alexander , Dreyer Viola , Sikhondze Welile , Dlamini Qiniso , DiNardo Andrew , Mtetwa Godwin , Lukhele Bhekumusa , Vambe Debrah , Lange Christoph , Glenn Dlamini Muyalo , Ness Tara , Mejia Rojelio , Kalsdorf Barbara , Heyckendorf Jan , Kuhns Martin , Maurer Florian P. , Dlamini Sindisiwe , Maphalala Gugu , Niemann Stefan , Mandalakas Anna
Published: May 2022

Background

Stool is an important diagnostic specimen for tuberculosis in populations who struggle to provide sputum, such as children or people living with HIV. However, the culture of Mycobacterium tuberculosis (M. tuberculosis) complex strains from stool perform poorly. This limits the opportunity for phenotypic drug resistance testing with this specimen. Therefore, reliable molecular methods are urgently needed for comprehensive drug resistance testing on stool specimens.

Methods

We evaluated the performance of targeted next-generation sequencing (tNGS, Deeplex® Myc-TB) for the detection of mutations associated with M. tuberculosis complex drug resistance on DNA isolated from stool specimens provided by participants from a prospective cohort of patients treated for tuberculosis in Eswatini (n = 66; 56 with and 10 participants without M. tuberculosis complex DNA detected in stool by real-time quantitative PCR), and an independent German validation cohort of participants with culture-confirmed tuberculosis (n = 21).

Results

The tNGS assay detected M. tuberculosis complex DNA in 38 of 56 (68%) samples; for 28 of 38 (74%) samples, a full M. tuberculosis complex drug resistance prediction report was obtained. There was a high degree of concordance with sputum phenotypic drug susceptibility results (κ = 0.82). The ability to predict resistance was concentration-dependent and successful in 7/10 (70%), 18/25 (72%), and 3/21 (14%) of samples with stool PCR concentration thresholds of > 100 femtogram per microliter (fg/μl), 1 to 100 fg/μl, and < 1 fg/μl, respectively (p = 0.0004). The German cohort confirmed these results and demonstrated a similarly high concordance between stool tNGS and sputum phenotypic drug susceptibility results (κ = 0.84).

Conclusions

tNGS can identify drug resistance from stool provided by tuberculosis patients. This affords the opportunity to obtain critical diagnostic information for tuberculosis patients who struggle to provide respiratory specimens.
Paradoxical venous air embolism detected with point-of-care ultrasound: a case report
Authors: Ruiz Avila Hector Andres , García-Araque Hans Fred , Acosta-Gutiérrez Estivalis
Published: May 2022

Venous air embolism (VAE) is an uncommon event consistent in the entrainment of air from any communication between the environment and the venous vasculature that could occur during central venous catheter (CVC) manipulation, and might trigger circulatory shock within minutes depending on the amount of air embolized. We present a case of a critical care patient who presented sudden clinical hemodynamic deterioration after the removal of central venous catheter. Hemodynamic evaluation with point-of-care ultrasound (POCUS) showed bubbles in both right and left heart cavities wherewith air embolism facilitated by heart septal defect was suspected. Therefore, the patient was reintubated, supported with vasopressors and a new CVC was inserted to proceed with air aspiration. Shortly after, the patient’s hemodynamic status improved in terms of vital signs stabilization. 6 h after the event with optimal perfusion markers and diminished sedation, the patient showed left hemiparesis therefore a cerebral magnetic resonance (MRI) was also performed showing hyperintensity in the right precentral gyrus, so ischemic stroke without hemorrhagic transformation diagnosis was made, because of paradoxical embolism. This case report demonstrates the value of POCUS application as a diagnostic tool in the hemodynamically unstable patient.
Contribution of a novel gene to lysergic acid amide synthesis in Metarhizium brunneum
Authors: Britton Kelcie N. , Steen Chey R. , Davis Kyle A. , Sampson Jessi K. , Panaccione Daniel G.
Published: May 2022

Objective

The fungus Metarhizium brunneum produces ergot alkaloids of the lysergic acid amide class, most abundantly lysergic acid α-hydroxyethylamide (LAH). Genes for making ergot alkaloids are clustered in the genomes of producers. Gene clusters of LAH-producing fungi contain an α/β hydrolase fold protein-encoding gene named easP whose presence correlates with LAH production but whose contribution to LAH synthesis in unknown. We tested whether EasP contributes to LAH accumulation through gene knockout studies.

Results

We knocked out easP in M. brunneum via a CRISPR/Cas9-based approach, and accumulation of LAH was reduced to less than half the amount observed in the wild type. Because LAH accumulation was reduced and not eliminated, we identified and mutated the only close homolog of easP in the M. brunneum genome, a gene we named estA. An easP/estA double mutant did not differ from the easP mutant in lysergic acid amide accumulation, indicating estA had no role in the pathway. We conclude EasP contributes to LAH accumulation but is not absolutely required. Either a gene encoding redundant function and lacking sequence identity with easP resides outside the ergot alkaloid synthesis gene cluster, or EasP plays an accessory role in the synthesis of LAH.
Differentially methylated CpGs in response to growth hormone administration in children with idiopathic short stature
Authors: Shao Xiaojian , Le Stunff Catherine , Cheung Warren , Kwan Tony , Lathrop Mark , Pastinen Tomi , Bougnères Pierre
Published: May 2022

Background

Recombinant human growth hormone (rhGH) has shown a great growth-promoting potential in children with idiopathic short stature (ISS). However, the response to rhGH differs across individuals, largely due to genetic and epigenetic heterogeneity. Since epigenetic marks on the methylome can be dynamically influenced by GH, we performed a comprehensive pharmacoepigenomics analysis of DNA methylation changes associated with long-term rhGH administration in children with ISS.

Results

We measured DNA methylation profiles before and after GH treatment (with a duration of ~ 18 months in average) on 47 healthy children using customized methylC-seq capture sequencing. Their changes were compared and associated with changes in plasma IGF1 by adjusting sex, age, treatment duration and estimated blood proportions. We observed a considerable inter-individual heterogeneity of DNA methylation changes responding to GH treatment. We identified 267 response-associated differentially methylated cytosines (DMCs) that were enriched in promoter regions, CpG islands and blood cell-type-specific regulatory elements. Furthermore, the genes associated with these DMCs were enriched in the biology process of “cell development,” “neuron differentiation” and “developmental growth,” and in the TGF-beta signaling pathway, PPAR Alpha pathway, endoderm differentiation pathway, adipocytokine signaling pathway as well as PI3K-Akt signaling pathway, and cAMP signaling pathway.

Conclusion

Our study provides a first insight in DNA methylation changes associated with rhGH administration, which may help understand mechanisms of epigenetic regulation on GH-responsive genes.
Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort
Authors: Grasset Leslie , Proust-Lima Cécile , Mangin Jean-François , Habert Marie-Odile , Dubois Bruno , Paquet Claire , Hanon Olivier , Gabelle Audrey , Ceccaldi Mathieu , Annweiler Cédric , David Renaud , Jonveaux Therese , Belin Catherine , Julian Adrien , Rouch-Leroyer Isabelle , Pariente Jérémie , Locatelli Maxime , Chupin Marie , Chêne Geneviève , Dufouil Carole ,   on behalf of the Memento Cohort Study group
Published: May 2022

Background

This work aimed to investigate the potential pathways involved in the association between social and lifestyle factors, biomarkers of Alzheimer’s disease and related dementia (ADRD), and cognition.

Methods

The authors studied 2323 participants from the Memento study, a French nationwide clinical cohort. Social and lifestyle factors were education level, current household incomes, physical activity, leisure activities, and social network from which two continuous latent variables were computed: an early to midlife (EML) and a latelife (LL) indicator. Brain magnetic resonance imaging (MRI), lumbar puncture, and amyloid-positron emission tomography (PET) were used to define three latent variables: neurodegeneration, small vessel disease (SVD), and AD pathology. Cognitive function was defined as the underlying factor of a latent variable with four cognitive tests. Structural equation models were used to evaluate cross-sectional pathways between social and lifestyle factors and cognition.

Results

Participants’ mean age was 70.9 years old, 62% were women, 28% were apolipoprotein-ε4 carriers, and 59% had a Clinical Dementia Rating (CDR) score of 0.5. Higher early to midlife social indicator was only directly associated with better cognitive function (direct β = 0.364 (0.322; 0.405), with no indirect pathway through ADRD biomarkers (total β = 0.392 (0.351; 0.429)). In addition to a direct effect on cognition (direct β = 0.076 (0.033; 0.118)), the association between latelife lifestyle indicator and cognition was also mostly mediated by an indirect effect through lower neurodegeneration (indirect β = 0.066 (0.042; 0.090) and direct β =  − 0.116 (− 0.153; − 0.079)), but not through AD pathology nor SVD.

Conclusions

Early to midlife social factors are directly associated with higher cognitive functions. Latelife lifestyle factors may help preserve cognitive functions through lower neurodegeneration.
The m6A methylation regulates gonadal sex differentiation in chicken embryo
Authors: Li Jianbo , Zhang Xiuan , Wang Xiqiong , Sun Congjiao , Zheng Jiangxia , Li Junying , Yi Guoqiang , Yang Ning
Published: May 2022

Background

As a ubiquitous reversible epigenetic RNA modification, N6-methyladenosine (m6A) plays crucial regulatory roles in multiple biological pathways. However, its functional mechanisms in sex determination and differentiation during gonadal development of chicken embryos are not clear. Therefore, we established a transcriptome-wide m6A map in the female and male chicken left gonads of embryonic day 7 (E7) by methylated RNA immunoprecipitation sequencing (MeRIP-seq) to offer insight into the landscape of m6A methylation and investigate the post-transcriptional modification underlying gonadal differentiation.

Results

The chicken embryonic gonadal transcriptome was extensively methylated. We found 15,191 and 16,111 m6A peaks in the female and male left gonads, respectively, which were mainly enriched in the coding sequence (CDS) and stop codon. Among these m6A peaks, we identified that 1013 and 751 were hypermethylated in females and males, respectively. These differential peaks covered 281 and 327 genes, such as BMP2, SMAD2, SOX9 and CYP19A1, which were primarily associated with development, morphogenesis and sex differentiation by functional enrichment. Further analysis revealed that the m6A methylation level was positively correlated with gene expression abundance. Furthermore, we found that YTHDC2 could regulate the expression of sex-related genes, especially HEMGN and SOX9, in male mesonephros/gonad mingle cells, which was verified by in vitro experiments, suggesting a regulatory role of m6A methylation in chicken gonad differentiation.

Conclusions

This work provided a comprehensive m6A methylation profile of chicken embryonic gonads and revealed YTHDC2 as a key regulator responsible for sex differentiation. Our results contribute to a better understanding of epigenetic factors involved in chicken sex determination and differentiation and to promoting the future development of sex manipulation in poultry industry.
The effectiveness of a feminist-informed, individualised counselling intervention for the treatment of eating disorders: a case series study
Authors: Tone Jessica , Chelius Belinda , Miller Yvette D.
Published: May 2022

Background

Currently, there is limited empirical validation of feminist-informed or individualised interventions for the treatment of eating disorders. The aim of this study was to examine the effectiveness of a feminist-informed, individually delivered counselling intervention for the treatment of eating disorders at a community-based eating disorder treatment service.

Methods

Eighty individuals aged between 17 and 64 years presenting to an outpatient eating disorder service were examined in a case series design at baseline, session 10, session 20 and end of treatment (session 30). Changes in eating disorder symptomology, depression, anxiety, stress, and mental health recovery over the course of treatment were examined in linear mixed model analyses.

Results

The treatment intervention was effective in reducing eating disorder symptomology and stress and improving mental health recovery after 10 sessions in a sample of 80 eating disorder participants engaged with the treatment service. Reductions in eating disorder symptomology and stress and improvements to mental health recovery were maintained at session 20 and session 30.

Conclusions

The findings of this study provide preliminary support for feminist-informed and individualised interventions for the treatment of eating disorders in community-based settings.
The who and what of validation: an experimental examination of validation and invalidation of specific emotions and the moderating effect of emotion dysregulation
Authors: Kuo Janice R. , Fitzpatrick Skye , Ip Jennifer , Uliaszek Amanda
Published: May 2022

Background

Theory and research indicate that validation is associated with reductions in negative emotions, whereas invalidation is associated with escalation of negative emotions. However, it remains unclear whether these effects are consistent across emotions, and/or moderated by an individual’s levels of emotion dysregulation. The present study experimentally examines the effects of validation and invalidation across emotions and as moderated by emotion dysregulation.

Methods

One hundred twenty-six participants completed a measure of emotion dysregulation, and then listened to a rejection-themed imagery script after which they reported the intensity of several emotions. Participants were then presented with either validating or invalidating feedback about their most intense self-reported emotion, depending on their counterbalancing order. They then repeated the procedure for the other condition. Self-reported negative emotions via continuous rating dial, heart rate (HR), and skin conductance level (SCL) were monitored throughout.

Results

Higher emotion dysregulation was associated with greater increases in self-reported positive emotion when shame or sadness was validated and lesser increases when fear was validated. There were no significant moderating effects of emotion dysregulation in response to invalidation for any emotion on any index.

Conclusions

The effects of validation appear emotion specific and dependent on levels of emotion dysregulation. These findings may help inform more strategic use of validation in psychotherapeutic interventions.
Influence of chemical and mineralogical soil properties on the adsorption of sulfamethoxazole and diclofenac in Mediterranean soils
Authors: De Mastro Francesco , Cacace Claudio , Traversa Andreina , Pallara Mauro , Cocozza Claudio , Mottola Francesca , Brunetti Gennaro
Published: May 2022

Background

The irrigation with treated wastewaters can be a way for the introduction of organic contaminants in soils. However, their adsorption onto soils can allow a control of their bioavailability and leaching. The adsorption is influenced by properties of contaminants (water solubility, chemical structure) and soils (organic matter content, pH, mineralogy). This study aimed to investigate the effect of mineralogical composition, organic matter content and others parameters of soils on the adsorption of sulfamethoxazole (SMX) and diclofenac (DCF), two contaminants of emerging concerns (CECs), in real cases (Altamura, Sibari and Noci soils).

Results

The isotherms data showed that the adsorption of the two CECs closely matched the Freundlich model, even if the DCF could also fit the linear one. The only exception was the adsorption of SMX on the soil of Sibari, for which Langmuir's model fitted better. In all cases, the Kd values were the highest for Altamura soil according mainly to its content of organic carbon. Positive correlations were found between Kd value of DCF and the soil organic carbon and Al oxyhydroxides content, suggesting their roles in its adsorption, while SMX showed only a slight positive correlation with the soil organic carbon content. Finally, between the two CECs studied, DCF was more adsorbed than SMX also because of the lower water solubility of the former.

Conclusions

The good interaction between DCF and soil organic carbon suggests the organic amendment of soils before the application of treated watewaters. The low adsorption of SMX onto soils suggests greater leaching of this compound which is, therefore, potentially more dangerous than DCF. For this reason, the application of a filtration system with appropriate adsorbent materials before the application of wastewater to soils should be expected.

Graphical Abstract