bluuebunny/crossref_metadata_2025 huggingface dataset:
Scedosporium infection disseminated “from toe to head” in allogeneic stem cell transplant recipient: a case report
Authors: Marinovic Debra A. , Bhaimia Eric , Forrest Graeme N. , LaRue Rebecca , Nathan Sunita , Ustun Celalettin , Ward Anna
Published: May 2023

Background

Scedosporium is a lesser-known non-Aspergillus genus of mold that can present in unsuspecting ways. If overlooked, it may disseminate and cause high mortality in high-risk allogeneic stem cell transplant recipients.

Case presentation

This case report describes a 65-year-old patient with Acute Myeloid Leukemia who underwent an allogeneic hematopoietic stem cell transplant after a period of prolonged neutropenia with fluconazole prophylaxis. She suffered severe debility with altered mentation from a S. apiospermum infection which likely disseminated from a toe wound to the lung and central nervous system. She was successfully treated with liposomal amphotericin B and voriconazole, but faced a prolonged recovery from physical and neurologic sequela.

Conclusions

The case highlights the importance of adequate anti-mold prophylaxis in high-risk patients, and the value of a thorough physical examination in this patient population, with particular attention to skin and soft tissue findings.
Clinical characteristics and antibiotic resistance profile of invasive MRSA infections in newborn inpatients: a retrospective multicenter study from China
Authors: Wu Xia , Wang Chuanqing , He Leiyan , Xu Hongmei , Jing Chunmei , Chen Yinghu , Deng Jikui , Lin Aiwei , Deng Huiling , Cai Huijun , Chen Yiping , Yang Jinhong , Zhang Ting , Cao Qing , Hao Jianhua , Huang Yuanyuan , Yu Hui
Published: May 2023

Background

Methicillin-resistant Staphylococcus aureus (MRSA) can cause invasive infections with significant mortality in neonates. This study aimed to analyze the clinical characteristics and antibiotic resistance profiles of invasive MRSA infections and determine risk factors associated with invasive MRSA infections in newborn inpatients.

Methods

This multicenter retrospective study of inpatients from eleven hospitals in the Infectious Diseases Surveillance of Pediatrics (ISPED) group of China was performed over a two-year period (2018–2019). Statistical significance was calculated by applying the χ2 test or by Fisher’s exact test in the case of small sample sizes.

Results

A total 220 patients were included. Among included cases, 67 (30.45%) were invasive MRSA infections, including two deaths (2.99%), while 153 (69.55%) were noninvasive infections. The invasive infections of MRSA occurred at a median age of 8 days on admission, which was significantly younger compared to 19 days in noninvasive cases. Sepsis (86.6%) was the most common invasive infection, followed by pneumonia (7.4%), bone and joint infections (3.0%), central nervous system infection (1.5%), and peritonitis (1.5%). Congenital heart disease, low birth weight infant (<2500 g), but not preterm neonates, and bronchopulmonary dysplasia, were more commonly found in invasive MRSA infections. All these isolates were susceptible to vancomycin and linezolid and were resistant to penicillin. Additionally, 69.37% were resistant to erythromycin, 57.66% to clindamycin, 7.04% to levofloxacin, 4.62% to sulfamethoxazole-trimethoprim, 4.29% to minocycline, 1.33% to gentamicin, and 3.13% were intermediate to rifampin.

Conclusion

Low age at admission (≤8 days), congenital heart disease, and low birth weight were associated with invasive MRSA infections in neonates, and no isolates resistant to vancomycin and linezolid were found. Determining these risks in suspected neonates may help identify patients with imminent invasive infections who may require intensive monitoring and therapy.
Economic evaluation of a community health worker model for tuberculosis care in Ho Chi Minh City, Viet Nam: a mixed-methods Social Return on Investment Analysis
Authors: Quang Vo Luan Nguyen , Forse Rachel Jeanette , Tran Jacqueline , Dam Thu , Driscoll Jenny , Codlin Andrew James , Creswell Jacob , Sidney-Annerstedt Kristi , Van Truong Vinh , Thi Minh Ha Dang , Huu Lan Nguyen , Nguyen Hoa Binh , Nguyen Nhung Viet
Published: May 2023

Background

There is extensive evidence for the cost-effectiveness of programmatic and additional tuberculosis (TB) interventions, but no studies have employed the social return on investment (SROI) methodology. We conducted a SROI analysis to measure the benefits of a community health worker (CHW) model for active TB case finding and patient-centered care.

Methods

This mixed-method study took place alongside a TB intervention implemented in Ho Chi Minh City, Viet Nam, between October-2017 – September-2019. The valuation encompassed beneficiary, health system and societal perspectives over a 5-year time-horizon. We conducted a rapid literature review, two focus group discussions and 14 in-depth interviews to identify and validate pertinent stakeholders and material value drivers. We compiled quantitative data from the TB program’s and the intervention’s surveillance systems, ecological databases, scientific publications, project accounts and 11 beneficiary surveys. We mapped, quantified and monetized value drivers to derive a crude financial benefit, which was adjusted for four counterfactuals. We calculated a SROI based on the net present value (NPV) of benefits and investments using a discounted cash flow model with a discount rate of 3.5%. A scenario analysis assessed SROI at varying discount rates of 0-10%.

Results

The mathematical model yielded NPVs of US$235,511 in investments and US$8,497,183 in benefits. This suggested a return of US$36.08 for each dollar invested, ranging from US$31.66-US39.00 for varying discount rate scenarios.

Conclusions

The evaluated CHW-based TB intervention generated substantial individual and societal benefits. The SROI methodology may be an alternative for the economic evaluation of healthcare interventions.
Barriers and facilitators of HPV vaccination in sub-saharan Africa: a systematic review
Authors: Kutz Jean-Marc , Rausche Pia , Gheit Tarik , Puradiredja Dewi Ismajani , Fusco Daniela
Published: May 2023

Background

Human Papilloma Virus (HPV) is the most common sexually transmitted infection worldwide. Globally, both men and women have a 50% risk of being infected at least once in their life. HPV prevalence is among the highest in sub-Saharan Africa (SSA), at an average of 24%. HPV causes different types of cancers, including cervical cancer (CC), which is the leading cause of cancer deaths among women in SSA. HPV-vaccination has been proven to be effective in reducing HPV induced cancers. SSA countries are delayed in reaching the WHO’s target of fully vaccinating 90% of girls within the age of 15 by 2030. Our systematic review aims to identify barriers and facilitators of HPV-vaccination in SSA to inform national implementation strategies in the region.

Methods

This is a mixed method systematic review based on the PRISMA statement and The Joanna Briggs Institute Reviewers’ Manual. Search strategies were adapted to each selected database: PubMed/MEDLINE, Livivo, Google Scholar, Science Direct, and African Journals Online for papers published in English, Italian, German, French and Spanish between 1 December 2011 and 31 December 2021. Zotero and Rayyan were the software used for data management. The appraisal was conducted by three independent reviewers.

Results

A total of 20 articles were selected for appraisal from an initial 536 articles. Barriers included: limited health system capacities, socio-economic status, stigma, fear and costs of vaccines, negative experience with vaccinations, COVID-19 pandemic, lack of correct information, health education (HE) and consent. Additionally, we found that boys are scarcely considered for HPV-vaccination by parents and stakeholders. Facilitators included: information and knowledge, policy implementation, positive experience with vaccinations, HE, stakeholders’ engagement, women’s empowerment, community engagement, seasonality, and target-oriented vaccination campaigns.

Conclusions

This review synthesizes barriers and facilitators of HPV-vaccinations in SSA. Addressing these can contribute to the implementation of more effective HPV immunization programs targeted at eliminating CC in line with the WHO 90/70/90 strategy.

Registration and funding

Protocol ID: CRD42022338609 registered in the International Prospective Register of Systematic Reviews (PROSPERO). Partial funds: German Centre for Infection research (DZIF) project NAMASTE: 8,008,803,819.
Effect modification by geographic area on the association between health literacy and self-rated health: a nationwide cross-sectional study in Japan
Authors: Ishikawa Hirono , Ogawa Runa , Otsuki Aki , Saito Junko , Yaguchi-Saito Akiko , Kuchiba Aya , Fujimori Maiko , Fukuda Yoshiharu , Shimazu Taichi ,   INFORM Study Group, Hayakawa Masayo , Hosono Satoyo , Inoue Manami , Kaji Yuki , Katanoda Kota , Matsuda Tomohiro , Matsuoka Yutaka J. , Odawara Miyuki , Takahashi Hirokazu , Takahashi Miyako , Uchitomi Yosuke , Umezawa Jun , Watanabe Otome , Yoshimi Itsuro , Kreps Gary L. , Sakurai Naomi , Momosaka Takumi , Akiyama Miki , Miyawaki Rina , Okubo Ryo , Akamatsu Rie , Kawasaki Yui , Fujisaki Kahori , Ogawa Luna , Imamura Haruhiko , Nakaya Kumi , Nakaya Naoki , Mitsutake Seigo , Sasai Hiroyuki
Published: May 2023

Background

Health literacy (HL) has gained increasing attention as a factor related to health behaviors and outcomes. This study aimed to investigate geographic differences in HL levels and effect modification by geographic area on their relationship with self-rated health in the Japanese population using a nationwide sample.

Methods

Data for this study were derived from a nationally representative cross-sectional survey on health information access for consumers in Japan using a mailed self-administered questionnaire in 2020 (INFORM Study 2020). Valid responses from 3,511 survey participants, selected using two-stage stratified random sampling, were analyzed in this study. HL was measured using the Communicative and Critical Health Literacy Scale (CCHL). Multiple regression and logistic regression analyses were conducted to examine the associations between geographic characteristics and HL and effect modification on the association between HL and self-rated health by geographic area, controlling for sociodemographic characteristics.

Results

The mean HL score was 3.45 (SD = 0.78), somewhat lower compared with previous studies on the Japanese general population. HL was higher in Kanto area than in Chubu area, after controlling for sociodemographic factors and municipality size. Furthermore, HL was positively associated with self-rated health after controlling for sociodemographic and geographic factors; however, this association was more evident in eastern areas than in western areas.

Conclusion

The findings indicate geographic differences in HL levels and effect modification by geographic area on the relationship between HL and self-rated health in the general Japanese population. HL was more strongly associated with self-rated health in eastern areas than in western areas. Further investigation is needed to explore the moderating effects of areal features, including the distribution of primary care physicians and social capital, when formulating strategies to improve HL in different contexts.
Risk of fracture according to temporal changes of low body weight changes in adults over 40 years: a nationwide population-based cohort study
Authors: Kim Jung Guel , Hong Jae-Young , Park Jiwon , Park Sang-Min , Han Kyungdo , Kim Ho-Joong , Yeom Jin S.
Published: May 2023

Background

Low body weight is associated with an increased risk of fractures. However, the effect of temporal changes in the low body weight status on the risk of fracture remains unknown. This study aimed to evaluate the relationships between temporal changes in low body weight status and the risk of fractures in adults over the age of 40 years.

Methods

This study included data on adults over 40 years old who underwent two biannual consecutive general health examinations between January 1, 2007 and December 31, 2009 extracted from the National Health Insurance Database, a large nationwide population database. Fracture cases in this cohort were monitored from the time of the last health examination to the end of the designated follow-up period (from January 1, 2010 to December 31, 2018) or the participant's death. Fractures were defined as any fracture resulting in hospitalization or outpatient treatment claim after the date of general health screening. The study population was then separated into four groups based on the temporal changes in low body weight status as follows: low body weight to low body weight (L-to-L), low body weight to non-low body weight (L-to-N), non-low body weight to low body weight (N-to-L), and non-low body weight to non-low body weight (N-to-N). The hazard ratios (HRs) for new fractures, depending on weight changes over time, were calculated using Cox proportional hazard analysis.

Results

Adults in the L-to-L, N-to-L, and L-to-N groups had a substantially increased risk of fractures after multivariate adjustment (HR, 1.165; 95% confidence interval [CI], 1.113–1.218; HR, 1.193; 95% CI, 1.131–1.259; and HR, 1.114; 95% CI, 1.050–1.183, respectively). Although the adjusted HR was greater in participants who changed into having a low body weight, followed by those with consistently low body weight, those with low body weight remained to have an elevated risk of fracture independent of weight fluctuation. Elderly men (aged over 65 years), high blood pressure, and chronic kidney disease were significantly associated with an increase in fractures (p < 0.05).

Conclusion

Individuals aged over 40 years with low body weight, even after regaining normal weight, had an increased risk of fracture. Moreover, having a low body weight after having a normal body weight increased the risk of fractures the most, followed by those with consistently low body weight.
Understanding volunteer motivations and concerns in coaching and officiating basketball: implications for sport policy
Authors: Casey Meghan , Harvey Jack , Charity Melanie , Talpey Scott , Reece Lindsey , Eime Rochelle
Published: May 2023

Sport participation and volunteering can make important contributions to good health. Sporting organisations need volunteers to deliver their participation opportunities and for many years the sector has faced challenges to volunteer recruitment and retention, especially due to the increased bureaucratic and compliance demands in operating community sports clubs. As sporting organisations pivot to adapt to COVID-safe sport we can learn about their experiences to inform volunteer recruitment and retention policies and practices. This research examined volunteer intentions and motivations in coaching and officiating in basketball and explored factors influencing their decision to return to COVID-safe basketball. Data was collected via an online survey that drew on theoretical frameworks of volunteer motivations (i.e. modified Volunteer Functions Inventory VFI) in sport as well as sport policies related to COVID-safe guidelines for return to sport. Data was collected in Victoria Australia during July 2020 before basketball had the chance to return from the first Australian-wide COVID-19 lockdown. Volunteers had positive intentions to return to basketball following COVID-19 restrictions because it was fun, to help others, or because friends/family were involved. Volunteers were most concerned that others will not comply with COVID-safe policies particularly around isolating when feeling unwell (95%), but also reported concerns about the inconveniences of some COVID-safe policies introduced to return to organised sport (e.g. social distancing, density limits, and enforcing rule changes). Understanding these volunteer intentions, motivations and factors influencing the decision to return to COVID-safe basketball can help inform recruitment and retention strategies to support volunteers in sport. Practical implications for sport policy and practice are discussed.
Effectiveness of spinal manipulation and biopsychosocial self-management compared to medical care for low back pain: a randomized trial study protocol
Authors: Bronfort Gert , Delitto Anthony , Schneider Michael , Heagerty Patrick J. , Chou Roger , Connett John , Evans Roni , George Steven , Glick Ronald M. , Greco Carol , Hanson Linda , Keefe Francis , Leininger Brent , Licciardone John , McFarland Christine , Meier Eric , Schulz Craig , Turk Dennis
Published: May 2023

Background

Chronic low back pain (cLBP) is widespread, costly, and burdensome to patients and health systems. Little is known about non-pharmacological treatments for the secondary prevention of cLBP. There is some evidence that treatments addressing psychosocial factors in higher risk patients are more effective than usual care. However, most clinical trials on acute and subacute LBP have evaluated interventions irrespective of prognosis.

Methods

We have designed a phase 3 randomized trial with a 2 × 2 factorial design. The study is also a Hybrid type 1 trial with focus on intervention effectiveness while simultaneously considering plausible implementation strategies. Adults (n = 1000) with acute/subacute LBP at moderate to high risk of chronicity based on the STarT Back screening tool will be randomized in to 1 of 4 interventions lasting up to 8 weeks: supported self-management (SSM), spinal manipulation therapy (SMT), both SSM and SMT, or medical care. The primary objective is to assess intervention effectiveness; the secondary objective is to assess barriers and facilitators impacting future implementation. Primary effectiveness outcome measures are: (1) average pain intensity over 12 months post-randomization (pain, numerical rating scale); (2) average low back disability over 12 months post-randomization (Roland-Morris Disability Questionnaire); (3) prevention of cLBP that is impactful at 10–12 months follow-up (LBP impact from the PROMIS-29 Profile v2.0). Secondary outcomes include: recovery, PROMIS-29 Profile v2.0 measures to assess pain interference, physical function, anxiety, depression, fatigue, sleep disturbance, and ability to participate in social roles and activities. Other patient-reported measures include LBP frequency, medication use, healthcare utilization, productivity loss, STarT Back screening tool status, patient satisfaction, prevention of chronicity, adverse events, and dissemination measures. Objective measures include the Quebec Task Force Classification, Timed Up & Go Test, the Sit to Stand Test, and the Sock Test assessed by clinicians blinded to the patients’ intervention assignment.

Discussion

By targeting those subjects at higher risk this trial aims to fill an important gap in the scientific literature regarding the effectiveness of promising non-pharmacological treatments compared to medical care for the management of patients with an acute episode of LBP and the prevention of progression to a severe chronic back problem.

Trial registration

ClinicalTrials.gov Identifier: NCT03581123.
A comparison of coblation and modified monopolar tonsillectomy in adults
Authors: Lou Zhengcai
Published: May 2023

Objective

To compare the intraoperative records and postoperative clinical outcomes of adults who underwent coblation and modified monopolar tonsillectomy tonsillectomies.

Materials and methods

Adult patients with tonsillectomy were randomly divided into the coblation and modified monopolar tonsillectomy groups. The estimated blood loss, postoperative pain score, operation time, post-tonsillectomy hemorrhage (PTH), and cost of disposable equipment were compared.

Results

Pain intensity in the coblation and monopolar groups was similar on postoperative days 3 and 7. However, the mean maximum pain score in the monopolar group was significantly higher compared to the coblation group on postoperative days 1 (P < 0.01) and 2 (P < 0.05).Secondary PTH occurred in 7.1% (23/326) of patients in the coblation group and 2.8% (9/327) of patients in the monopolar group (P < 0.05).

Conclusion

Although pain was significantly increased on postoperative days 1 and 2 in the modified monopolar tonsillectomy group, the operation time, secondary PTH, and medical costs were significantly decreased compared to the coblation technique group.
Association between lipid metabolism and periodontitis in obese patients: a cross-sectional study
Authors: Jia Ru , Zhang Yuwei , Wang Zhiyu , Hu Bo , Wang Zhenzhen , Qiao Hu
Published: May 2023

Background

To investigate the association between clinical periodontal parameters of periodontitis, serum lipid metabolism markers and adipokines’ levels in patients with obesity and periodontitis.

Methods

A total of 112 patients admitted to Hospital of Xi’an Jiaotong University were included in this study. They were divided into normal body weight group (18.5 < body mass index, BMI < 25, n = 36), overweight group (25 ≤ BMI < 30, n = 38), and obesity group (BMI ≥ 30, n = 38) accordingly. The diagnosis of periodontitis was based on the newest international classification of periodontitis. Full-mouth clinical periodontal measurements included: plaque index, periodontal pocket depth, clinical attachment level, and bleeding on probing. Gingival crevicular fluid samples were analyzed for: Interleukin-1β, tumor necrosis factor-α, Interleukin-6 and C-reactive protein. Serum triglycerides, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and glycosylated hemoglobin levels were measured. Visfatin, leptin, resistin, and adiponectin levels in serum were also measured.

Results

The ratio of participants without periodontitis was significantly highest in normal weight group, and the proportion of severe periodontitis (stage III and IV) was highest in obesity group. The periodontal pocket depth, clinical attachment level, and the inflammatory cytokines in gingival crevicular fluid in obesity group and overweight group were higher than those in normal body weight group. The BMI and waist-to-hip ratio (WHR) were significantly positive correlated with periodontal pocket depth and clinical attachment level. Using a Multivariate logistic regression model, periodontitis correlates to BMI, WHR, serum levels of triglyceride, total cholesterol, low density lipoprotein, and adipokines such as visfatin, leptin, and resistin.

Conclusions

Obesity is positively correlated with the aggravation of periodontitis. Obesity may aggravate the damage to periodontal tissue by regulating the secretion level of adipokines.
Evaluation of micronuclei and antioxidant status in hospital radiation workers occupationally exposed to low-dose ionizing radiation
Authors: Mousavikia S. N. , Bahreyni Toossi M. T. , Khademi S. , Soukhtanloo M. , Azimian H.
Published: May 2023

Purpose

There is scientific evidence that ionizing radiation (IR) can be responsible for various health hazards that are one of the concerns in occupational exposure. This study was performed to evaluate DNA damage and antioxidant status in hospital workers who are occupationally exposed to low doses of IR.

Materials and methods

In this study, twenty occupationally exposed to low doses of IR (CT and angiography) comprising with control groups which matched them. In order to investigate the effects of chronic irradiation of radiation workers, Micronuclei (MN) frequency and the antioxidant activity of Superoxide Dismutase (SOD), Catalase (CAT) and Total Antioxidant Capacity (TAC) were measured. Then, to check adaptation against high challenge dose, the samples (in all groups) were irradiated in vitro and MN frequency was compared. Finally, to investigated the effect of the high dose after the acute and chronic low dose of ionizing radiation, MN frequency was compared in two groups (the control group that was to in-vitro irradiated (acute low dose + high dose) and radiation workers (chronic low dose + high dose)).

Results

MN frequency in the occupationally exposed group (n = 30) increased significantly when compared to the control group (p-value < 0.0001). However, chronic irradiation of radiation workers could not lead to an adaptive Sresponse, while acute low-doses could produce this effect (p-value ˂ 0.05). In addition, the activity levels of antioxidant enzymes SOD, CAT, and TAC were not statistically different between the radiation workers and the control group (p-value > 0.05).

Conclusions

We observed that exposure to low doses of IR leads to increased cytogenetic damage, could not cause an adaptive-response, and improve antioxidant capacity in radiation workers. Controlling healthcare workers' exposure is the first step to improving the health of hospital workers and the quality of patient care, thus decreasing human and economic costs.
Circular RNAs arising from synaptic host genes during human neuronal differentiation are modulated by SFPQ RNA-binding protein
Authors: Watts Michelle E. , Oksanen Marika , Lejerkrans Sanna , Mastropasqua Francesca , Gorospe Myriam , Tammimies Kristiina
Published: May 2023

Background

Circular RNA (circRNA) molecules, generated through non-canonical back-splicing of exon-exon junctions, have recently been implicated in diverse biological functions including transcriptional regulation and modulation of protein interactions. CircRNAs are emerging as a key component of the complex neural transcriptome implicated in brain development. However, the specific expression patterns and functions of circRNAs in human neuronal differentiation have not been explored.

Results

Using total RNA sequencing analysis, we identified expressed circRNAs during the differentiation of human neuroepithelial stem (NES) cells into developing neurons and discovered that many circRNAs originated from host genes associated with synaptic function. Interestingly, when assessing population data, exons giving rise to circRNAs in our dataset had a higher frequency of genetic variants. Additionally, screening for RNA-binding protein sites identified enrichment of Splicing Factor Proline and Glutamine Rich (SFPQ) motifs in increased circRNAs, several of which were reduced by SFPQ knockdown and enriched in SFPQ ribonucleoprotein complexes.

Conclusions

Our study provides an in-depth characterisation of circRNAs in a human neuronal differentiation model and highlights SFPQ as both a regulator and binding partner of circRNAs elevated during neuronal maturation.
Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials
Authors: Patikorn Chanthawat , Saidoung Pantakarn , Pham Tuan , Phisalprapa Pochamana , Lee Yeong Yeh , Varady Krista A. , Veettil Sajesh K. , Chaiyakunapruk Nathorn
Published: May 2023

Background

Systematic reviews and meta-analyses of randomized clinical trials (RCTs) have reported the benefits of ketogenic diets (KD) in various participants such as patients with epilepsy and adults with overweight or obesity. Nevertheless, there has been little synthesis of the strength and quality of this evidence in aggregate.

Methods

To grade the evidence from published meta-analyses of RCTs that assessed the association of KD, ketogenic low-carbohydrate high-fat diet (K-LCHF), and very low-calorie KD (VLCKD) with health outcomes, PubMed, EMBASE, Epistemonikos, and Cochrane database of systematic reviews were searched up to February 15, 2023. Meta-analyses of RCTs of KD were included. Meta-analyses were re-performed using a random-effects model. The quality of evidence per association provided in meta-analyses was rated by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) criteria as high, moderate, low, and very low.

Results

We included 17 meta-analyses comprising 68 RCTs (median [interquartile range, IQR] sample size of 42 [20–104] participants and follow-up period of 13 [8–36] weeks) and 115 unique associations. There were 51 statistically significant associations (44%) of which four associations were supported by high-quality evidence (reduced triglyceride (n = 2), seizure frequency (n = 1) and increased low-density lipoprotein cholesterol (LDL-C) (n = 1)) and four associations supported by moderate-quality evidence (decrease in body weight, respiratory exchange ratio (RER), hemoglobin A1c, and increased total cholesterol). The remaining associations were supported by very low (26 associations) to low (17 associations) quality evidence. In overweight or obese adults, VLCKD was significantly associated with improvement in anthropometric and cardiometabolic outcomes without worsening muscle mass, LDL-C, and total cholesterol. K-LCHF was associated with reduced body weight and body fat percentage, but also reduced muscle mass in healthy participants.

Conclusions

This umbrella review found beneficial associations of KD supported by moderate to high-quality evidence on seizure and several cardiometabolic parameters. However, KD was associated with a clinically meaningful increase in LDL-C. Clinical trials with long-term follow-up are warranted to investigate whether the short-term effects of KD will translate to beneficial effects on clinical outcomes such as cardiovascular events and mortality.
The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study
Authors: Li Yan , Liu Hongyan , Ye Shuting , Zhang Bumei , Li Xiaopei , Yuan Jiapei , Du Yongrui , Wang Jianmei , Yang Yang
Published: May 2023

Background

Endometriosis is recognized as a complex gynecological disorder that can cause severe pain and infertility, affecting 6–10% of all reproductive-aged women. Endometriosis is a condition in which endometrial tissue, which normally lines the inside of the uterus, deposits in other tissues. The etiology and pathogenesis of endometriosis remain ambiguous. Despite debates, it is generally agreed that endometriosis is a chronic inflammatory disease, and patients with endometriosis appear to be in a hypercoagulable state. The coagulation system plays important roles in hemostasis and inflammatory responses. Therefore, the purpose of this study is to use publicly available GWAS summary statistics to examine the causal relationship between coagulation factors and the risk of endometriosis.

Methods

To investigate the causal relationship between coagulation factors and the risk of endometriosis, a two-sample Mendelian randomization (MR) analytic framework was used. A series of quality control procedures were followed in order to select eligible instrumental variables that were strongly associated with the exposures (vWF, ADAMTS13, aPTT, FVIII, FXI, FVII, FX, ETP, PAI-1, protein C, and plasmin). Two independent cohorts of European ancestry with endometriosis GWAS summary statistics were used: UK Biobank (4354 cases and 217,500 controls) and FinnGen (8288 cases and 68,969 controls). We conducted MR analyses separately in the UK Biobank and FinnGen, followed by a meta-analysis. The Cochran’s Q test, MR-Egger intercept test, and leave-one-out sensitivity analyses were used to assess the heterogeneities, horizontal pleiotropy, and stabilities of SNPs in endometriosis.

Results

Our two-sample MR analysis of 11 coagulation factors in the UK Biobank suggested a reliable causal effect of genetically predicted plasma ADAMTS13 level on decreased endometriosis risk. A negative causal effect of ADAMTS13 and a positive causal effect of vWF on endometriosis were observed in the FinnGen. In the meta-analysis, the causal associations remained significant with a strong effect size. The MR analyses also identified potential causal effects of ADAMTS13 and vWF on different sub-phenotypes of endometrioses.

Conclusions

Our MR analysis based on GWAS data from large-scale population studies demonstrated the causal associations between ADAMTS13/vWF and the risk of endometriosis. These findings suggest that these coagulation factors are involved in the development of endometriosis and may represent potential therapeutic targets for the management of this complex disease.
Adipsin alleviates cardiac microvascular injury in diabetic cardiomyopathy through Csk-dependent signaling mechanism
Authors: Zhang Xuebin , Duan Yu , Zhang Xiao , Jiang Mengyuan , Man Wanrong , Zhang Yan , Wu Dexi , Zhang Jiye , Song Xinglong , Li Congye , Lin Jie , Sun Dongdong
Published: May 2023

Background

Microvascular complications are associated with an overtly increased risk of adverse outcomes in patients with diabetes including coronary microvascular injury which manifested as disruption of adherens junctions between cardiac microvascular endothelial cells (CMECs). However, particular mechanism leading to diabetic coronary microvascular hyperpermeability remains elusive.

Methods

Experimental diabetes was induced in mice with adipose tissue-specific Adipsin overexpression (AdipsinLSL/LSL-Cre) and their respective control (AdipsinLSL/LSL). In addition, cultured CMECs were subjected to high glucose/palmitic acid (HG + PA) treatment to simulate diabetes for a mechanistic approach.

Results

The results showed that Adipsin overexpression significantly reduced cardiac microvascular permeability, preserved coronary microvascular integrity, and increased coronary microvascular density. Adipsin overexpression also attenuated cardiac dysfunction in diabetic mice. E/A ratio, an indicator of cardiac diastolic function, was improved by Adipsin. Adipsin overexpression retarded left ventricular adverse remodeling, enhanced LVEF, and improved cardiac systolic function. Adipsin-enriched exosomes were taken up by CMECs, inhibited CMECs apoptosis, and increased CMECs proliferation under HG + PA treatment. Adipsin-enriched exosomes also accelerated wound healing, rescued cell migration defects, and promoted tube formation in response to HG + PA challenge. Furthermore, Adipsin-enriched exosomes maintained adherens junctions at endothelial cell borders and reversed endothelial hyperpermeability disrupted by HG + PA insult. Mechanistically, Adipsin blocked HG + PA-induced Src phosphorylation (Tyr416), VE-cadherin phosphorylation (Tyr685 and Tyr731), and VE-cadherin internalization, thus maintaining CMECs adherens junctions integrity. LC-MS/MS analysis and co-immunoprecipitation analysis (Co-IP) unveiled Csk as a direct downstream regulator of Adipsin. Csk knockdown increased Src phosphorylation (Tyr416) and VE-cadherin phosphorylation (Tyr685 and Tyr731), while abolishing Adipsin-induced inhibition of VE-cadherin internalization. Furthermore, Csk knockdown counteracted Adipsin-induced protective effects on endothelial hyperpermeability in vitro and endothelial barrier integrity of coronary microvessels in vivo.

Conclusions

Together, these findings favor the vital role of Adipsin in the regulation of CMECs adherens junctions integrity, revealing its promises as a treatment target against diabetic coronary microvascular dysfunction.

Graphical Abstract

Graphical abstract depicting the mechanisms of action behind Adipsin-induced regulation of diabetic coronary microvascular dysfunction.
Biomechanics of open-globe injury: a review
Authors: Wang Songtao , Li Fuqiang , Jin Siyan , Zhang Yu , Yang Ning , Zhao Jinsong
Published: May 2023

Open-globe injury is a common cause of blindness clinically caused by blunt trauma, sharp injury, or shock waves, characterised by rupture of the cornea or sclera and exposure of eye contents to the environment. It causes catastrophic damage to the globe, resulting in severe visual impairment and psychological trauma to the patient. Depending on the structure of the globe, the biomechanics causing ocular rupture can vary, and trauma to different parts of the globe can cause varying degrees of eye injury. The weak parts or parts of the eyeball in contact with foreign bodies rupture when biomechanics, such as external force, unit area impact energy, corneoscleral stress, and intraocular pressure exceed a certain value. Studying the biomechanics of open-globe injury and its influencing factors can provide a reference for eye-contact operations and the design of eye-protection devices. This review summarises the biomechanics of open-globe injury and the relevant factors.
Bioengineered stem cell membrane functionalized nanoparticles combine anti-inflammatory and antimicrobial properties for sepsis treatment
Authors: Lu Lu , Quan Lingli , Li Jian , Yuan Junbin , Nie Xinmin , Huang Xueyuan , Dong Hang , Su Yanrong , Huang Yufen , Kou Qingjie , Liu Leping , Liu Haiting , Zhou Xionghui , Gui Rong , Gu Lan
Published: May 2023

Background

Sepsis is a syndrome of physiological, pathological and biochemical abnormalities caused by infection. Although the mortality rate is lower than before, many survivors have persistent infection, which means sepsis calls for new treatment. After infection, inflammatory mediators were largely released into the blood, leading to multiple organ dysfunction. Therefore, anti-infection and anti-inflammation are critical issues in sepsis management.

Results

Here, we successfully constructed a novel nanometer drug loading system for sepsis management, FZ/MER-AgMOF@Bm. The nanoparticles were modified with LPS-treated bone marrow mesenchymal stem cell (BMSC) membrane, and silver metal organic framework (AgMOF) was used as the nanocore for loading FPS-ZM1 and meropenem which was delivery to the infectious microenvironments (IMEs) to exert dual anti-inflammatory and antibacterial effects. FZ/MER-AgMOF@Bm effectively alleviated excessive inflammatory response and eliminated bacteria. FZ/MER-AgMOF@Bm also played an anti-inflammatory role by promoting the polarization of macrophages to M2. When sepsis induced by cecal ligation and puncture (CLP) challenged mice was treated, FZ/MER-AgMOF@Bm could not only reduce the levels of pro-inflammatory factors and lung injury, but also help to improve hypothermia caused by septic shock and prolong survival time.

Conclusions

Together, the nanoparticles played a role in combined anti-inflammatory and antimicrobial properties, alleviating cytokine storm and protecting vital organ functions, could be a potential new strategy for sepsis management.
Carbon dots induce pathological damage to the intestine via causing intestinal flora dysbiosis and intestinal inflammation
Authors: Jia Mengmeng , Yi Bingcheng , Chen Xian , Xu Yongzhi , Xu Xinkai , Wu Zhaoxu , Ji Jing , Tang Jinglong , Yu Dianke , Zheng Yuxin , Zhou Qihui , Zhao Yanjie
Published: May 2023

Background

Carbon dots (CDs), as excellent antibacterial nanomaterials, have gained great attention in treating infection-induced diseases such as periodontitis and stomatitis. Given the eventual exposure of CDs to the intestine, elucidating the effect of CDs on intestinal health is required for the safety evaluation of CDs.

Results

Herein, CDs extracted from ε-poly-l-lysine (PL) were chosen to explore the modulation effect of CDs on probiotic behavior in vitro and intestinal remodeling in vivo. Results verify that PL-CDs negatively regulate Lactobacillus rhamnosus (L. rhamnosus) growth via increasing reactive oxygen species (ROS) production and reducing the antioxidant activity, which subsequently destroys membrane permeability and integrity. PL-CDs are also inclined to inhibit cell viability and accelerate cell apoptosis. In vivo, the gavage of PL-CDs is verified to induce inflammatory infiltration and barrier damage in mice. Moreover, PL-CDs are found to increase the Firmicutes to Bacteroidota (F/B) ratio and the relative abundance of Lachnospiraceae while decreasing that of Muribaculaceae.

Conclusion

Overall, these evidences indicate that PL-CDs may inevitably result in intestinal flora dysbiosis via inhibiting probiotic growth and simultaneously activating intestinal inflammation, thus causing pathological damage to the intestine, which provides an effective and insightful reference for the potential risk of CDs from the perspective of intestinal remodeling.
Tricyclic antidepressants induce liver inflammation by targeting NLRP3 inflammasome activation
Authors: Mu Wenqing , Xu Guang , Wang Zhilei , Li Qiang , Sun Siqiao , Qin Qin , Li Zhiyong , Shi Wei , Dai Wenzhang , Zhan Xiaoyan , Wang Jiabo , Bai Zhaofang , Xiao Xiaohe
Published: May 2023

Background

Idiosyncratic drug-induced liver injury (IDILI) is common in hepatology practices and, in some cases, lethal. Increasing evidence show that tricyclic antidepressants (TCAs) can induce IDILI in clinical applications but the underlying mechanisms are still poorly understood.

Methods

We assessed the specificity of several TCAs for NLRP3 inflammasome via MCC950 (a selective NLRP3 inhibitor) pretreatment and Nlrp3 knockout (Nlrp3−/−) BMDMs. Meanwhile, the role of NLRP3 inflammasome in the TCA nortriptyline-induced hepatotoxicity was demonstrated in Nlrp3−/− mice.

Results

We reported here that nortriptyline, a common TCA, induced idiosyncratic hepatotoxicity in a NLRP3 inflammasome-dependent manner in mildly inflammatory states. In parallel in vitro studies, nortriptyline triggered the inflammasome activation, which was completely blocked by Nlrp3 deficiency or MCC950 pretreatment. Furthermore, nortriptyline treatment led to mitochondrial damage and subsequent mitochondrial reactive oxygen species (mtROS) production resulting in aberrant activation of the NLRP3 inflammasome; a selective mitochondrial ROS inhibitor pretreatment dramatically abrogated nortriptyline-triggered the NLRP3 inflammasome activation. Notably, exposure to other TCAs also induced aberrant activation of the NLRP3 inflammasome by triggering upstream signaling events.

Conclusion

Collectively, our findings revealed that the NLRP3 inflammasome may act as a crucial target for TCA agents and suggested that the core structures of TCAs may contribute to the aberrant activation of NLRP3 inflammasome induced by them, an important factor involved in the pathogenesis of TCA-induced liver injury.
METTL3 and STAT3 form a positive feedback loop to promote cell metastasis in hepatocellular carcinoma
Authors: Liu Bowen , Cao Jinling , Wu Biting , Hao Kaixuan , Wang Xiangyun , Chen Xin , Shen Zhifa
Published: May 2023

Background

It is well-established that most Hepatocellular carcinoma (HCC) patients die of metastasis, yet the potential mechanisms orchestrating metastasis remain poorly understood. Current evidence suggests that the dysregulation of METTL3-mediated m6A methylation modification is closely associated with cancer progression. STAT3 is an oncogenic transcription factor that reportedly plays a central role in the occurrence and development of HCC. However, the relationship between METTL3 and STAT3 in HCC metastasis remains unclear.

Methods

The relationship between METTL3 expression and the survival of HCC patients was assessed by online tools GEPIA and Kaplan–Meier Plotter. Western blotting, Tissue microarray (TMA), and immunohistochemistry (IHC) staining were used to evaluate the expression levels of METTL3 and STAT3 in HCC cell lines and metastatic and non-metastatic tissues. Methylated RNA immunoprecipitation (MeRIP), MeRIP sequencing (MeRIP-seq), qRT-PCR, RNA immunoprecipitation (RIP), Western blotting and luciferase reporter gene assay were utilized to clarify the mechanism of METTL3 regulating STAT3 expression. Immunofluorescence staining, Western blotting, qRT-PCR, Co-immunoprecipitation (Co-IP), IHC staining, TMA and Chromatin immunoprecipitation (ChIP) assay were performed to explore the mechanism of STAT3 modulating METTL3 localization. Cell viability, wound healing and transwell assay, and orthotopic xenograft model were used to evaluate the role of METTL3-STAT3 feedback loop in the promotion of HCC metastasis in vitro and in vivo.

Results

METTL3 and STAT3 are both abundantly expressed in high-metastatic HCC cells and tissues. Moreover, a positive correlation was found between the expression of STAT3 and METTL3 in HCC tissues. Mechanistically, METTL3 could induce the m6A modification of STAT3 mRNA, and then promote the translation of m6A-contained STAT3 mRNA by interacting with the translation initiation machinery. In contrast, STAT3 promoted nuclear localization of METTL3 via transcriptionally upregulating WTAP, a vital member of the methyltransferase complex, and facilitated the methyltransferase function of METTL3. METTL3 and STAT3 form a positive feedback loop to accelerate HCC metastasis in vitro and in vivo.

Conclusions

Our findings reveal a novel mechanism of HCC metastasis and uncover the METTL3-STAT3 feedback signaling as a potential target for the anti-metastatic treatment of HCC.
Mitochondrial transplantation as a novel therapeutic strategy for cardiovascular diseases
Authors: Sun Mingchu , Jiang Wenhua , Mu Nan , Zhang Zihui , Yu Lu , Ma Heng
Published: May 2023

Cardiovascular disease (CVD) is the leading cause of noncommunicable disease-related death worldwide, and effective therapeutic strategies against CVD are urgently needed. Mitochondria dysfunction involves in the onset and development of CVD. Nowadays, mitochondrial transplantation, an alternative treatment aimed at increasing mitochondrial number and improving mitochondrial function, has been emerged with great therapeutic potential. Substantial evidence indicates that mitochondrial transplantation improves cardiac function and outcomes in patients with CVD. Therefore, mitochondrial transplantation has profound implications in the prevention and treatment of CVD. Here, we review the mitochondrial abnormalities that occur in CVD and summarize the therapeutic strategies of mitochondrial transplantation for CVD.
The potential role of scavenging flies as mechanical vectors of Lagovirus europaeus/GI.2
Authors: Lopes Ana M. , Almeida Tereza , Diz Sílvia , Côrte-Real João V. , Osório Hugo C. , Ramilo David W. , Rebelo Maria Teresa , da Fonseca Isabel Pereira , Esteves Pedro J. , Alves Paulo C. , Santos Nuno , Abrantes Joana
Published: May 2023

The European rabbit (Oryctolagus cuniculus) populations of the Iberian Peninsula have been severely affected by the emergence of the rabbit haemorrhagic disease virus (RHDV) Lagovirus europaeus/GI.2 (RHDV2/b). Bushflies and blowflies (Muscidae and Calliphoridae families, respectively) are important RHDV vectors in Oceania, but their epidemiological role is unknown in the native range of the European rabbit. In this study, scavenging flies were collected between June 2018 and February 2019 in baited traps at one site in southern Portugal, alongside a longitudinal capture-mark-recapture study of a wild European rabbit population, aiming to provide evidence of mechanical transmission of GI.2 by flies. Fly abundance, particularly from Calliphoridae and Muscidae families, peaked in October 2018 and in February 2019. By employing molecular tools, we were able to detect the presence of GI.2 in flies belonging to the families Calliphoridae, Muscidae, Fanniidae and Drosophilidae. The positive samples were detected during an RHD outbreak and absent in samples collected when no evidence of viral circulation in the local rabbit population was found. We were able to sequence a short viral genomic fragment, confirming its identity as RHDV GI.2. The results suggest that scavenging flies may act as mechanical vectors of GI.2 in the native range of the southwestern Iberian subspecies O. cuniculus algirus. Future studies should better assess their potential in the epidemiology of RHD and as a tool for monitoring viral circulation in the field.