bluuebunny/crossref_metadata_2025 huggingface dataset:
Appropriate dose of intravitreal ranibizumab for ROP: a retrospective study
Authors: Chen Yingying , Wang Shaoli , Chen Siying , Chen Xingyue , Han Lizhen , Zhong Qionglei , Zhang Kaiyan
Published: June 2022

Objective

To compare the recurrence rate of retinopathy of prematurity (ROP) after treatment with 0.3 mg vs. 0.25 mg ranibizumab.

Subjects

All patients with ROP who underwent intravitreal injection of ranibizumab in Hainan General Hospital between January 2014 and May 2020 were included in this retrospective study.

Methods

Eighty-two cases (146 eyes) who received intravitreal injection of 0.25 mg ranibizumab were included in the conventional-dose group, and 59 cases (108 eyes) who received intravitreal injection of 0.3 mg ranibizumab were included in the high-dose group. The two groups were further divided into the 25-28-week, 29-31-week, 32-34-week, and 35-36-week GA subgroups. The differences between the conventional-dose group and the high-dose group in gestational age (GA), birth weight (BW), age at initial injection (weeks), incidence of systemic diseases, the recurrence rate of ROP, and age at retinal vascularization completed (weeks) were analyzed.

Results

GA, BW, age at initial injection, and the incidence of systemic diseases were not significantly different between the conventional-dose group and the high-dose group (p > 0.05). The recurrence rates of ROP were significantly lower in the 25-28-week, 29-31-week, and 32-34-week subgroups of the high-dose group than in the same subgroups of the conventional-dose group (p < 0.05). Within the conventional-dose group, the recurrence rate of ROP was significantly lower in the 32-34-week and 35-36-week subgroups than in the 25-28-week and 29-31-week subgroups (p < 0.05). Within the high-dose group, the recurrence rate of ROP was not significantly different between the four subgroups (p > 0.05). Retinal vascularization was completed at a later age in the 32-34-week subgroup of the high-dose group than in the 32-34-week subgroup of the conventional-dose group (p < 0.05) but was not significantly different between the two groups at any other GA range (p > 0.05). No severe ocular or systemic complications occurred in any patient.

Conclusion

Treatment with 0.3 mg ranibizumab can reduce the recurrence rate of ROP without prolonging retinal vascularization or causing serious systemic complications. Therefore, this dose may be an appropriate therapeutic dose for ROP.
Effects of resilience on impulsivity, cognition and depression during protracted withdrawal among Chinese male methamphetamine users
Authors: He He , Zhou Siyao , Peng Chenhui , Ran Wang , Tong Siyu , Hong Lan , Cai Fangfang , Jin Wei , Jiang Yile , Li Mengjia , Wang Xuanping , Luo Mengdan , Wang Wei , Zhao Ke
Published: June 2022

Background

Methamphetamine (METH) dependence is a complex and dynamic public health problem. Long-term abuse of METH can increase numerous risks of mental and physical problems. Currently, the methods to reduce METH dependence and improve the withdrawal symptoms are limited and ineffective. Resilience is seen as a multidimensional and dynamic capability to recover or bounce back from stressful events and is also generally considered as a protective factor against mental dysfunction.

Methods

One hundred thirty-four males with METH dependence were consecutively recruited from Huanglong Compulsory Isolated Detoxification Center between 2019 and 2021, of whom 112 were into the group. The Connor-Davidson Resilience Scale (CD-RISC), Self-rating depression scale (SDS), Self-rating anxiety scale (SAS), Barratt Impulsiveness Scale-11(BIS-11), and the Repeatable Battery for the Assessment of Neuropsychological Status (Rbans) were used to evaluate resilience, depression, anxiety, impulsivity, and cognition respectively.

Results

The results mainly indicated that high resilience group showed lower SDS, SAS and BIS-11 scores than low resilience group (all p < 0.05). Besides, the total scores of Rbans were higher in high resilience groups than low resilience group (both p < 0.05). Moreover, linear regression results showed that resilience may be influenced by the scores of SDS and SAS.

Conclusions

Resilience is negatively correlated with impulsivity and depression. Besides, it is also positively associated with cognitive function. Drug users with higher resilience may have a strong ability to mobilize psychological resources to create a good psychological environment, which may have a positive effect on the relief or improvement of symptoms.
A structural equation model of the relationship among occupational stress, coping styles, and mental health of pediatric nurses in China: a cross-sectional study
Authors: Zhou Yating , Guo Xiaoli , Yin Huaying
Published: June 2022

Background

Pediatric nurses experience a wide rang of stressful events at work every day, which can trigger a lot of emotional responses. The objectives of this study were mainly to explore the potential interrelationships of occupational stress, coping styles and mental health among pediatric nurse.

Methods

A total of 381 pediatric nurses from Chongqing, China were recruited in this cross-sectional study. We performed this study based on a questionnaire survey that contained the Chinese Perceived Stress Scale (CPSS), Simplified Coping Style Questionnaire and Symptom-Checklist 90(SCL-90).

Results

The pediatric nurses reported having health risk stress(HRS) was 54.3%, and nurses with different medical professional titles, style of coping and profiles of mental health had significantly different occupational stress levels (P < 0.01). And with the application of the Spearman correlation analysis and Structural Equation Modelling were revealed a significant relationship among occupational stress, coping style and mental health. The positive coping style had a negative direct predictive effect on occupational stress (β = -0.499, P < 0.01) and mental health symptoms (β = -0.115, P < 0.01), negative coping styles had positive predictive effect on occupational stress (β = 0.185, P < 0.01) and mental health symptoms (β = 0.205, P < 0.01). Occupational stress had significant impact on mental health symptoms (β = 0.416, P < 0.01), and it was played a part of mediating effect between coping style and mental health.

Conclusion

These findings demonstrated significant associations between occupational stress, coping style and mental health in pediatric nurses, and this SEM model highlighted that the potential prediction effects of occupational stress and coping styles for mental health and the mediated effect of occupational stress between coping style and mental health, which we believe facilitates the understanding of these associations. This model should be useful in the formulation of strategies to improve mental health level for this population.
Using the multiphase optimization strategy (MOST) framework to optimize an intervention to increase COVID-19 testing for Black and Latino/Hispanic frontline essential workers: A study protocol
Authors: Gwadz Marya , Cleland Charles M. , Lizardo Maria , Hawkins Robert L. , Bangser Greg , Parameswaran Lalitha , Stanhope Victoria , Robinson Jennifer A. , Karim Shristi , Hollaway Tierra , Ramirez Paola G. , Filippone Prema L. , Ritchie Amanda S. , Banfield Angela , Silverman Elizabeth
Published: June 2022

Background

Among those at highest risk for COVID-19 exposure is the large population of frontline essential workers in occupations such food service, retail, personal care, and in-home health services, among whom Black and Latino/Hispanic persons are over-represented. For those not vaccinated and at risk for exposure to COVID-19, including frontline essential workers, regular (approximately weekly) COVID-19 testing is recommended. However, Black and Latino/Hispanic frontline essential workers in these occupations experience serious impediments to COVID-19 testing at individual/attitudinal- (e.g., lack of knowledge of guidelines), social- (e.g., social norms), and structural-levels of influence (e.g., poor access), and rates of testing for COVID-19 are insufficient.

Methods/design

The proposed community-engaged study uses the multiphase optimization strategy (MOST) framework and an efficient factorial design to test four candidate behavioral intervention components informed by an integrated conceptual model that combines critical race theory, harm reduction, and self-determination theory. They are A) motivational interview counseling, B) text messaging grounded in behavioral economics, C) peer education, and D) access to testing (via navigation to an appointment vs. a self-test kit). All participants receive health education on COVID-19. The specific aims are to: identify which components contribute meaningfully to improvement in the primary outcome, COVID-19 testing confirmed with documentary evidence, with the most effective combination of components comprising an “optimized” intervention that strategically balances effectiveness against affordability, scalability, and efficiency (Aim 1); identify mediators and moderators of the effects of components (Aim 2); and use a mixed-methods approach to explore relationships among COVID-19 testing and vaccination (Aim 3). Participants will be N = 448 Black and Latino/Hispanic frontline essential workers not tested for COVID-19 in the past six months and not fully vaccinated for COVID-19, randomly assigned to one of 16 intervention conditions, and assessed at 6- and 12-weeks post-baseline. Last, N = 50 participants will engage in qualitative in-depth interviews.

Discussion

This optimization trial is designed to yield an effective, affordable, and efficient behavioral intervention that can be rapidly scaled in community settings. Further, it will advance the literature on intervention approaches for social inequities such as those evident in the COVID-19 pandemic.

Trial registration

ClinicalTrials.gov: NCT05139927; Registered on 11/29/2021. Protocol version 1.0. May 2, 2022, Version 1.0
Global and national burden and trends of mortality and disability-adjusted life years for silicosis, from 1990 to 2019: results from the Global Burden of Disease study 2019
Authors: Chen Shimin , Liu Miao , Xie Fei
Published: June 2022

Background

Silicosis, as an important type of pneumoconiosis, leads to progressive and irreversible conditions from the beginning of inflammation and fibrosis. However, the data on the global burden of silicosis and long-term trends were limited.

Methods

Derived from the Global Burden of Disease study 2019 (online publicly available: Global Health Data Exchange), data on both crude and age-standardized rates (ASR) per 100,00 people of mortality and disability-adjusted life years (DALYs) due to silicosis was collected and analyzed. The burden and trends of mortality and DALYs due to silicosis was assessed by 204 countries and territories, by 5-year interval of age group and by sex from 1990 to 2019. And all the regions were divided into 5 categories according to Sociodemographic Index (SDI). Temporal trends in mortality and DALY were evaluated only to ASR by the Joinpoint regression model.

Results

More than 12.9 thousand [95% Uncertainty Intervals (UI): 10.9, 16.2] death cases occurred due to silicosis worldwide, and 655.7 thousand (95% UI: 519.3, 828.0) DALYs were attributed to silicosis in 2019. From 1990 to 2019, global number of mortality and DALYs in countries with high SDI quintile decreased by 0.35% (95% UI: − 0.45, − 0.17) and 0.32% (95% UI: − 0.45, − 0.01), respectively. There was a greater burden in low- and middle-income countries were estimated in 2019 according to ASRs. The global number of mortality and DALYs among males accounted for over 95% of all in 2019. Both age-sex-specific mortality and DALY rate were increasing with aging and reached their peak at 85–89 age group. During the past 30 years, ASR of mortality and DALYs showed a decreasing trend with average annual percentage change at -3.0% [95% Confidence Intervals (CI): − 3.2, − 2.9] and − 2.0 (95% CI: − 1.7, − 2.2), respectively.

Conclusions

Silicosis remains an important health issue and causes a potentially serious burden worldwide. Attention should be paid to making preventable, affordable and effective measures in lower SDI regions.
Occupational cold exposure and symptoms of carpal tunnel syndrome – a population-based study
Authors: Stjernbrandt Albin , Vihlborg Per , Wahlström Viktoria , Wahlström Jens , Lewis Charlotte
Published: June 2022

Background

Cold exposure is an underrecognized occupational hazard that may increase the risk of peripheral nerve entrapment. The aim of this study was to determine if self-reported occupational exposure to contact and ambient cooling was associated with symptoms of carpal tunnel syndrome (CTS).

Methods

In this mainly cross-sectional study, surveys were conducted on a population-based sample of men and women between 18 and 70 years of age, living in northern Sweden. Cold exposure and presence of symptoms suggestive of CTS were subjectively reported. Associations between exposure and outcome were evaluated using logistic regression.

Results

The study included 2,703 women and 2,314 men, with a median age of 60 years (interquartile range 19). Symptoms of CTS were reported by 453 (9.2%). Being highly occupationally exposed (almost always) to contact cooling of the hands was associated with reporting CTS (OR 3.20; 95% CI 1.62–6.33), as was ambient cooling (OR 2.00; 95% CI 1.03–3.88) and severe ambient cooling (OR 4.02 95% CI 2.09–7.71), after adjusting for age, gender, body mass index, current daily smoking, diabetes mellitus, joint disease, and hand-arm vibration exposure. The point estimates increased with longer daily exposure duration. For workers exposed to severe ambient cooling for more than half of their working hours, in addition to performing heavy manual handling every day, the OR for reporting CTS was 7.25 (95% CI 3.88–13.53), with a positive additive interaction effect (expressed as relative excess risk due to interaction) of 4.67.

Conclusions

Self-reported occupational exposure to contact and ambient cooling was associated with symptoms suggestive of CTS. There were statistically significant positive exposure–response patterns for time spent exposed to contact and ambient cooling at work in relation to reporting symptoms of CTS. Positive additive interaction effects between cold exposure and heavy manual handling were also found. Since there was important potential uncontrolled confounding regarding repetitive wrist movements and forceful gripping, the results need to be confirmed by other studies, preferably with longitudinal design and more detailed exposure assessment.
The beneficial effects of square dance on musculoskeletal system in early postmenopausal Chinese women: a cross-sectional study
Authors: Sun Jie , Yao Chen , Wang Ziping , Wu Jiancheng , Zhang Bo , Zhou Zhenyu , Liu Fan , Zhang Yafeng
Published: June 2022

Background

This study was set to investigate the correlation between square dance and musculoskeletal system of early postmenopausal Chinese women.

Methods

Chinese postmenopausal women, who had been without menstruation for 1–10 years from the onset of menopause were recruited from community centers for this study. A standardized structured face-to-face interview was performed to collect demographic information, life styles, personal medical history, diet and menstrual status. Subjects who had been practicing regular square dance without participated in other sports activities for more than 2 years and over 4 h per week (usually more than 45 min per time and more than 5 times per week) were assigned to square dance group. Those postmenopausal women who had not participated in regular exercises (no more than 0.5 h per week) were recruited as the sedentary control group. Bone mineral density (BMD) of spine, total hip and femoral neck was measured by using dual-energy X-ray absorptiometry. Lower limb muscle strength was measured for the non-dominant leg, body flexibility was measured by a simple trunk bend-and-reach test, and body balance was evaluated using a single-stance test for the non-dominant leg. Independent two-tailed Student’s t-test was used for data analysis.

Results

152 subjects from community centers were selected for this study and divided into square dance group (n = 74) and control group (n = 78). The square dance subjects had higher lumbar spine BMD (p = 0.01) and total hip BMD (p = 0.02) than control subjects, but there was no significant difference of femoral neck BMD (p = 0.48) between these two groups. Functional testing indicated that square dance subjects had higher lower limb muscle strength (p < 0.01) and longer single-stance time (p = 0.02) than the control subjects, but there was no significant difference in trunk bend-and-reach (p = 0.12) between these two groups.

Conclusion

Our results show that postmenopausal Chinese women can get beneficial effects, like higher BMD, stronger lower limb muscle and improved body balance ability on musculoskeletal system by participating in square dance regularly.
Solution structure of the type I polyketide synthase Pks13 from Mycobacterium tuberculosis
Authors: Bon Cécile , Cabantous Stéphanie , Julien Sylviane , Guillet Valérie , Chalut Christian , Rima Julie , Brison Yoann , Malaga Wladimir , Sanchez-Dafun Angelique , Gavalda Sabine , Quémard Annaïk , Marcoux Julien , Waldo Geoffrey S. , Guilhot Christophe , Mourey Lionel
Published: June 2022

Background

Type I polyketide synthases (PKSs) are multifunctional enzymes responsible for the biosynthesis of a group of diverse natural compounds with biotechnological and pharmaceutical interest called polyketides. The diversity of polyketides is impressive despite the limited set of catalytic domains used by PKSs for biosynthesis, leading to considerable interest in deciphering their structure‐function relationships, which is challenging due to high intrinsic flexibility. Among nineteen polyketide synthases encoded by the genome of Mycobacterium tuberculosis, Pks13 is the condensase required for the final condensation step of two long acyl chains in the biosynthetic pathway of mycolic acids, essential components of the cell envelope of Corynebacterineae species. It has been validated as a promising druggable target and knowledge of its structure is essential to speed up drug discovery to fight against tuberculosis.

Results

We report here a quasi-atomic model of Pks13 obtained using small-angle X-ray scattering of the entire protein and various molecular subspecies combined with known high-resolution structures of Pks13 domains or structural homologues. As a comparison, the low-resolution structures of two other mycobacterial polyketide synthases, Mas and PpsA from Mycobacterium bovis BCG, are also presented. This study highlights a monomeric and elongated state of the enzyme with the apo- and holo-forms being identical at the resolution probed. Catalytic domains are segregated into two parts, which correspond to the condensation reaction per se and to the release of the product, a pivot for the enzyme flexibility being at the interface. The two acyl carrier protein domains are found at opposite sides of the ketosynthase domain and display distinct characteristics in terms of flexibility.

Conclusions

The Pks13 model reported here provides the first structural information on the molecular mechanism of this complex enzyme and opens up new perspectives to develop inhibitors that target the interactions with its enzymatic partners or between catalytic domains within Pks13 itself.
Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive
Authors: O’Brien Nicole F. , Fonseca Yudy , Johnson Hunter C. , Postels Douglas , Birbeck Gretchen L. , Chimalizeni Yamikani , Seydel Karl B. , Bernard Gushu Montfort , Phiri Tusekile , June Sylvester , Chetcuti Karen , Vidal Lorenna , Goyal Manu S. , Taylor Terrie E.
Published: June 2022

Background

Cerebral malaria (CM) results in significant paediatric death and neurodisability in sub-Saharan Africa. Several different alterations to typical Transcranial Doppler Ultrasound (TCD) flow velocities and waveforms in CM have been described, but mechanistic contributors to these abnormalities are unknown. If identified, targeted, TCD-guided adjunctive therapy in CM may improve outcomes.

Methods

This was a prospective, observational study of children 6 months to 12 years with CM in Blantyre, Malawi recruited between January 2018 and June 2021. Medical history, physical examination, laboratory analysis, electroencephalogram, and magnetic resonance imaging were undertaken on presentation. Admission TCD results determined phenotypic grouping following a priori definitions. Evaluation of the relationship between haemodynamic, metabolic, or intracranial perturbations that lead to these observed phenotypes in other diseases was undertaken. Neurological outcomes at hospital discharge were evaluated using the Paediatric Cerebral Performance Categorization (PCPC) score.

Results

One hundred seventy-four patients were enrolled. Seven (4%) had a normal TCD examination, 57 (33%) met criteria for hyperaemia, 50 (29%) for low flow, 14 (8%) for microvascular obstruction, 11 (6%) for vasospasm, and 35 (20%) for isolated posterior circulation high flow. A lower cardiac index (CI) and higher systemic vascular resistive index (SVRI) were present in those with low flow than other groups (p < 0.003), though these values are normal for age (CI 4.4 [3.7,5] l/min/m2, SVRI 1552 [1197,1961] dscm-5m2). Other parameters were largely not significantly different between phenotypes. Overall, 118 children (68%) had a good neurological outcome. Twenty-three (13%) died, and 33 (19%) had neurological deficits. Outcomes were best for participants with hyperaemia and isolated posterior high flow (PCPC 1–2 in 77 and 89% respectively). Participants with low flow had the least likelihood of a good outcome (PCPC 1–2 in 42%) (p < 0.001). Cerebral autoregulation was significantly better in children with good outcome (transient hyperemic response ratio (THRR) 1.12 [1.04,1.2]) compared to a poor outcome (THRR 1.05 [0.98,1.02], p = 0.05).

Conclusions

Common pathophysiological mechanisms leading to TCD phenotypes in non-malarial illness are not causative in children with CM. Alternative mechanistic contributors, including mechanical factors of the cerebrovasculature and biologically active regulators of vascular tone should be explored.
How does informal employment affect health and health equity? Emerging gaps in research from a scoping review and modified e-Delphi survey
Authors: Lee Juyeon , Di Ruggiero Erica
Published: June 2022

Introduction

This article reports on the results from a scoping review and a modified e-Delphi survey with experts which aimed to synthesize existing knowledge and identify research gaps on the health and health equity implications of informal employment in both low- and middle-income countries (LMICs) and high-income countries (HICs).

Methods

The scoping review included peer-reviewed articles published online between January 2015 and December 2019 in English. Additionally, a modified e-Delphi survey with experts was conducted to validate our findings from the scoping review and receive feedback on additional research and policy gaps. We drew on micro- and macro-level frameworks on employment relations and health inequities developed by the Employment Conditions Knowledge Network to synthesize and analyze existing literature.

Results

A total of 540 articles were screened, and 57 met the eligibility criteria for this scoping review study, including 36 on micro-level research, 19 on macro-level research, and 13 on policy intervention research. Most of the included studies were conducted in LMICs while the research interest in informal work and health has increased globally. Findings from existing literature on the health and health equity implications of informal employment are mixed: informal employment does not necessarily lead to poorer health outcomes than formal employment. Although all informal workers share some fundamental vulnerabilities, including harmful working conditions and limited access to health and social protections, the related health implications vary according to the sub-groups of workers (e.g., gender) and the country context (e.g., types of welfare state or labour market). In the modified e-Delphi survey, participants showed a high level of agreement on a lack of consensus on the definition of informal employment, the usefulness of the concept of informal employment, the need for more comparative policy research, qualitative health research, and research on the intersection between gender and informal employment.

Conclusions

Our results clearly identify the need for more research to further understand the various mechanisms through which informal employment affects health in different countries and for different groups of informal workers.
Composition tunability of semiconductor radiosensitizers for low-dose X-ray induced photodynamic therapy
Authors: Chen Lei , Zhang Jinghui , Xu Lihua , Zhu Luchao , Jing Jinpeng , Feng Yushuo , Wang Zongzhang , Liu Peifei , Sun Wenjing , Liu Xiangmei , Li Yimin , Chen Hongmin
Published: June 2022

Radiation therapy is one of the most commonly used methods in clinical cancer treatment, and radiosensitizers could achieve enhanced therapeutic efficacy by incorporating heavy elements into structures. However, the secondary excitation of these high-Z elements-doped nanosensitizers still imply intrinsic defects of low efficiency. Herein, we designed Bi-doped titanium dioxide nanosensitizers in which high-Z Bi ions with adjustable valence state (Bi3+or Bi4+) replaced some positions of Ti4+of anatase TiO2, increasing both X-rays absorption and oxygen vacancies. The as-prepared TiO2:Bi nanosensitizers indicated high ionizing radiation energy-transfer efficiency and photocatalytic activity, resulting in efficient electron–hole pair separation and reactive oxygen species production. After further modification with cancer cell targeting peptide, the obtained nanoplatform demonstrated good performance in U87MG cell uptakes and intracellular radicals-generation, severely damaging the vital subcellular organs of U87MG cells, such as mitochondrion, membrane lipid, and nuclei etc.These combined therapeutic actions mediated by the composition-tunable nanosensitizers significantly inhibited the U87MG tumor growth, providing a refreshing strategy for X-ray induced dynamic therapy of malignant tumors.
Investigating the influence of institutions, politics, organizations, and governance on the COVID-19 response in British Columbia, Canada: a jurisdictional case study protocol
Authors: Brubacher Laura Jane , Hasan Md. Zabir , Sriram Veena , Keidar Shelly , Wu Austin , Cheng Michael , Lovato Chris Y. ,   U. B. C. Working Group on Health Systems Response to COVID-19, Berman Peter
Published: June 2022

Background

Research on public health responses to COVID-19 globally has largely focused on understanding the virus’ epidemiology, identifying interventions to curb transmission, and assessing the impact of interventions on outcomes. Only recently have studies begun to situate their findings within the institutional, political, or organizational contexts of jurisdictions. Within British Columbia (BC), Canada, the COVID-19 response in early 2020 was deemed highly coordinated and effective overall; however, little is understood as to how these upstream factors influenced policy decisions.

Methods

Using a conceptual framework we developed, we are conducting a multidisciplinary jurisdictional case study to explore the influence of institutional (I), political (P), organizational (O), and governance (G) factors on BC’s COVID-19 public health response in 2020–2021. A document review (e.g. policy documents, media reports) is being used to (1) characterize relevant institutional and political factors in BC, (2) identify key policy decisions in BC’s epidemic progression, (3) create an organizational map of BC’s public health system structure, and (4) identify key informants for interviews. Quantitative data (e.g. COVID-19 case, hospitalization, death counts) from publicly accessible sources will be used to construct BC’s epidemic curve. Key informant interviews (n = 15–20) will explore governance processes in the COVID-19 response and triangulate data from prior procedures. Qualitative data will be analysed using a hybrid deductive–inductive coding approach and framework analysis. By integrating all of the data streams, our aim is to explore decision-making processes, identify how IPOG factors influenced policy decisions, and underscore implications for decision-making in public health crises in the BC context and elsewhere. Knowledge users within the jurisdiction will be consulted to construct recommendations for future planning and preparedness.

Discussion

As the COVID-19 pandemic evolves, governments have initiated retrospective examinations of their policies to identify lessons learned. Our conceptual framework articulates how interrelations between IPOG contextual factors might be applied to such analysis. Through this jurisdictional case study, we aim to contribute findings to strengthen governmental responses and improve preparedness for future health crises. This protocol can be adapted to and applied in other jurisdictions, across subnational jurisdictions, and internationally.
Epstein–Barr virus tegument protein BGLF2 in exosomes released from virus-producing cells facilitates de novo infection
Authors: Sato Yoshitaka , Yaguchi Masahiro , Okuno Yusuke , Ishimaru Hanako , Sagou Ken , Ozaki Somi , Suzuki Takeshi , Inagaki Tomoki , Umeda Miki , Watanabe Takahiro , Fujimuro Masahiro , Murata Takayuki , Kimura Hiroshi
Published: June 2022

Background

Viruses must adapt to the environment of their host cells to establish infection and persist. Diverse mammalian cells, including virus-infected cells, release extracellular vesicles such as exosomes containing proteins and miRNAs, and use these vesicles to mediate intercellular communication. However, the roles of exosomes in viral infection remain unclear.

Results

We screened viral proteins to identify those responsible for the exosome-mediated enhancement of Epstein–Barr virus (EBV) infection. We identified BGLF2 protein encapsulated in exosomes, which were released by EBV-infected cells. BGLF2 protein is a tegument protein that exists in the space between the envelope and nucleocapsid, and it is released into the cytoplasm shortly after infection. BGLF2 protein-containing exosomes enhanced viral gene expression and repressed innate immunity, thereby supporting the EBV infection.

Conclusions

The EBV tegument protein BGLF2 is encapsulated in exosomes and released by infected cells to facilitate the establishment of EBV infection. These findings suggest that tegument proteins support viral infection not only between the envelope and nucleocapsid, as well as in extraviral particles such as exosomes.

Graphical abstract
Blocking TIGIT/CD155 signalling reverses CD8+ T cell exhaustion and enhances the antitumor activity in cervical cancer
Authors: Liu Lu , Wang Aihong , Liu Xiaoli , Han Sai , Sun Yu , Zhang Junhua , Guo Lingyu , Zhang Youzhong
Published: June 2022

Objective

TIGIT/CD155 has attracted widespread attention as a new immune checkpoint and a potential target for cancer immunotherapy. In our study, we evaluated the role of TIGIT/CD155 checkpoints in the progression of cervical cancer.

Methods

The expression of CD155 and TIGIT in cervical cancer tissues was detected using flow cytometry, immunohistochemistry (IHC) and gene expression profiling. In vivo and in vitro experiments have proven that blocking TIGIT/CD155 restores the ability of CD8+T cells to produce cytokines. Changes in the NF-κB and ERK pathways were detected using western blotting (WB) after blocking TIGIT/CD155 signalling.

Results

TIGIT expression was elevated in patients with cervical cancer. High TIGIT expression in CD8+T lymphocytes from patients with cervical cancer promotes the exhaustion of CD8+T lymphocytes. In addition, CD155 is expressed at high levels in cervical cancer tissues and is negatively correlated with the level of infiltrating CD8+T cells. We found that TIGIT, upon binding to CD155 and being phosphorylated, inhibited NF-κB and ERK activation by recruiting SHIP-1, resulting in the downregulation of cytokine production. Blocking TIGIT in activated CD8+T cells attenuates the inhibitory effect of SHIP-1 on CD8+T cells and enhances the activation of NF-κB and ERK. In vivo and in vitro experiments have proven that blocking TIGIT/CD155 restores the ability of CD8+T cells to produce cytokines. Injecting the blocking antibody TIGIT in vivo inhibits tumour growth and enhances CD8+T lymphocyte function. Treatment with a combination of TIGIT and PD-1 inhibitors further increases the efficacy of the TIGIT blocking antibody.

Conclusions

Our research shows that TIGIT/CD155 is a potential therapeutic target for cervical cancer.
The treatment of Qibai Pingfei Capsule on chronic obstructive pulmonary disease may be mediated by Th17/Treg balance and gut-lung axis microbiota
Authors: Jia Yu , He Tiantian , Wu Di , Tong Jiabing , Zhu Jie , Li Zegeng , Dong Jingcheng
Published: June 2022

Background

Chronic obstructive pulmonary disease (COPD), a prevalent, progressive respiratory disease, has become the third leading cause of death globally. Increasing evidence suggests that intestinal and pulmonary microbiota dysbiosis is associated with COPD. Researchers have shown that T helper (Th) 17/regulatory T (Treg) imbalance is involved in COPD. Qibai Pingfei Capsule (QBPF) is a traditional Chinese medicine used to treat COPD clinically in China. However, the effects of QBPF intervention on the Th17/Treg balance and microbiota in the gut and lung are still poorly understood.

Methods

This study divided the rats into three groups (n = 8): control, model, and QBPF group. After establishing the model of COPD for four weeks and administering of QBPF for two weeks, Th17 cells, Treg cells, their associated cytokines, transcription factors, and intestinal and pulmonary microbiota of rats were analyzed. Furthermore, the correlations between intestinal and pulmonary microbiota and between bacterial genera and pulmonary function and immune function were measured.

Results

The results revealed that QBPF could improve pulmonary function and contribute to the new balance of Th17/Treg in COPD rats. Meanwhile, QBPF treatment could regulate the composition of intestinal and pulmonary microbiota and improve community structure in COPD rats, suppressing the relative abundance of Coprococcus_2, Prevotella_9, and Blautia in the gut and Mycoplasma in the lung, but accumulating the relative abundance of Prevotellaceae_UCG_003 in the gut and Rikenellaceae_RC9_gut_group in the lung. Additionally, gut–lung axis was confirmed by the significant correlations between the intestinal and pulmonary microbiota. Functional analysis of microbiota showed amino acid metabolism was altered in COPD rats in the gut and lung. Spearman correlation analysis further enriched the relationship between the microbiota in the gut and lung and pulmonary function and immune function in COPD model rats.

Conclusions

Our study indicated that the therapeutic effects of QBPF may be achieved by maintaining the immune cell balance and regulating the gut-lung axis microbiota, providing references to explore the potential biomarkers of COPD and the possible mechanism of QBPF to treat COPD.
Biomechanical effects of interbody cage height on adjacent segments in patients with lumbar degeneration: a 3D finite element study
Authors: Lu Xiao , Li Dachuan , Wang Hongli , Xia Xinlei , Ma Xiaosheng , Lv Feizhou , Zou Fei , Jiang Jianyuan
Published: June 2022

Objective

To investigate the biomechanical effects of interbody cage height on adjacent segments in patients with lumbar degeneration undergoing transforaminal lumbar interbody fusion (TLIF) surgery, so as to provide references for selection of interbody cage.

Methods

The finite element model of normal lower lumbar spine (L3–S1) was built and validated, then constructed three different degenerative segments in L3–L4, and the cages with different height (8, 10, 12, 14 mm) were implanted into L4–L5 disc. All the twelve models were loaded with pure moment of 7.5 N m to produce flexion, extension, lateral bending and axial rotation motions on lumbar spine, and the effects of cage height on range of motion (RoM) and intervertebral pressure in lumbar spine were investigated.

Results

The RoM of adjacent segments and the maximum stress of intervertebral discs increased with the increase in cage height, but this trend was not obvious in mild and moderate degeneration groups. After implantation of four different height cages (8, 10, 12, 14 mm), the RoM of L3/L4 segment reached the maximum during extension. The RoM of mild degeneration group was 2.07°, 2.45°, 2.48°, 2.54°, that of moderate degeneration group was 1.79°, 1.97°, 2.05°, 2.05°, and that of severe degeneration group was 1.43°, 1.66°, 1.74°, 1.74°. The stress of L3–L4 intervertebral disc reached the maximum during flexion. The maximum stress of L3–L4 intervertebral disc was 20.16 MPa, 20.28 MPa, 20.31 MPa and 20.33 MPa in the mild group, 20.58 MPa, 20.66 MPa, 20.71 MPa and 20.75 MPa in the moderate group, and 21.27 MPa, 21.40 MPa, 21.50 MPa and 21.60 MPa in the severe group.

Conclusion

For patients with mild-to-moderate lumbar degenerative disease who need to undergo TLIF surgery, it is recommended that the height of fusion cage should not exceed the original intervertebral space height by 2 mm, while for patients with severe degeneration, a fusion cage close to the original intervertebral height should be selected as far as possible, and the intervertebral space should not be overstretched.
Fluid challenge in critically ill patients receiving haemodynamic monitoring: a systematic review and comparison of two decades
Authors: Messina Antonio , Calabrò Lorenzo , Pugliese Luca , Lulja Aulona , Sopuch Alexandra , Rosalba Daniela , Morenghi Emanuela , Hernandez Glenn , Monnet Xavier , Cecconi Maurizio
Published: June 2022

Introduction

Fluid challenges are widely adopted in critically ill patients to reverse haemodynamic instability. We reviewed the literature to appraise fluid challenge characteristics in intensive care unit (ICU) patients receiving haemodynamic monitoring and considered two decades: 2000–2010 and 2011–2021.

Methods

We assessed research studies and collected data regarding study setting, patient population, fluid challenge characteristics, and monitoring. MEDLINE, Embase, and Cochrane search engines were used. A fluid challenge was defined as an infusion of a definite quantity of fluid (expressed as a volume in mL or ml/kg) in a fixed time (expressed in minutes), whose outcome was defined as a change in predefined haemodynamic variables above a predetermined threshold.

Results

We included 124 studies, 32 (25.8%) published in 2000–2010 and 92 (74.2%) in 2011–2021, overall enrolling 6,086 patients, who presented sepsis/septic shock in 50.6% of cases. The fluid challenge usually consisted of 500 mL (76.6%) of crystalloids (56.6%) infused with a rate of 25 mL/min. Fluid responsiveness was usually defined by a cardiac output/index (CO/CI) increase ≥ 15% (70.9%). The infusion time was quicker (15 min vs 30 min), and crystalloids were more frequent in the 2011–2021 compared to the 2000–2010 period.

Conclusions

In the literature, fluid challenges are usually performed by infusing 500 mL of crystalloids bolus in less than 20 min. A positive fluid challenge response, reported in 52% of ICU patients, is generally defined by a CO/CI increase ≥ 15%. Compared to the 2000–2010 decade, in 2011–2021 the infusion time of the fluid challenge was shorter, and crystalloids were more frequently used.
Intensity of insecticide resistance in the major malaria vector Anopheles funestus from Chikwawa, rural Southern Malawi
Authors: Kumala Justin , Koekemoer Lizette L. , Coetzee Maureen , Mzilahowa Themba
Published: June 2022

Background

Malaria vector control using insecticide-based approaches has proven to be an effective strategy. However, widespread insecticide resistance among malaria vector populations across sub-Saharan Africa threatens to derail control efforts. This study was conducted in Chikwawa district, an area in rural southern Malawi characterised by persistent malaria transmission and reports of insecticide resistance in the local mosquito population. The aim of the was to characterise the intensity of insecticide resistance within a population of Anopheles funestus sensu lato (s.l.), a major vector of malaria in this district.

Methods

Live adult females belonging to the An. funestus group were collected from households by indoor aspiration. The CDC bottle assay was used for phenotypic quantification of resistance to deltamethrin, permethrin and alpha-cypermethrin at 1×, 2.5×, 5× and 10× the recommended diagnostic dose for each of these insecticides. WHO tube assays were used to determine susceptibility to bendiocarb, dichlorodiphenyltrichloroethane (DDT) and pirimiphos-methyl insecticides at diagnostic concentrations.

Results

Anopheles funestus s.l. exposed to 10× the recommended diagnostic dose was highly resistant to alpha-cypermethrin (mortality 95.4%); in contrast, mortality was 100% when exposed to both deltamethrin and permethrin at the same dose. Despite showing susceptibility to deltamethrin and permethrin at the 10× concentration, mortality at the 5× concentration was 96.7% and 97.1%, respectively, indicating moderate resistance to these two insecticides. WHO susceptibility assays indicated strong resistance against bendiocarb (mortality 33.8%, n = 93), whereas there was full susceptibility to DDT (mortality 98.9%, n = 103) and pirimiphos-methyl (mortality 100%, n = 103).

Conclusions

Strategies for managing resistance to insecticides, particularly against pyrethroids, must be urgently implemented to maintain the effectiveness of insecticide-based vector control interventions in the area. Such strategies include the wide-scale introduction of third-generation synergist insecticide-treated bed nets (ITNs) and next-generation dual active ingredient ITNs. The use of effective non-pyrethroids, such as pirimiphos-methyl, clothianidin and potentially DDT, could provide a window of opportunity for indoor residual spraying across the district. This strategy would support the current Malawi Insecticide Resistance Management Plan which aims at rotating insecticides to minimise selection pressure and slow down the evolution of resistance to approved insecticides. These actions will help to prevent malaria vector control failure and improve progress towards malaria elimination.

Graphical Abstract
Sensitivity of wMel and wAlbB Wolbachia infections in Aedes aegypti Puducherry (Indian) strains to heat stress during larval development
Authors: Gunasekaran Kasinathan , Sadanandane Candasamy , Panneer Devaraju , Kumar Ashwani , Rahi Manju , Dinesh Sundaram , Vijayakumar Balakrishnan , Krishnaraja Muthuraman , Subbarao Sarala K. , Jambulingam Purushothaman
Published: June 2022

Background

ICMR-Vector Control Research Centre, Puducherry, India, developed two colonies ofAedes aegyptiinfected withwMel andwAlbBWolbaciastrains calledAe. aegypti(Pud) lines for dengue control. The sensitivity ofwMel andwAlbB strains inAe. aegypti(Pud) lines to heat stress was studied.

Methods

wMel andwAlbB infected and uninfectedAe. aegyptilarvae (first to fourth instars) were reared in the laboratory to adults at 26 °C, 30 °C, 36 °C and 40 °C constant temperatures and also 26–30 °C, 26–36 °C and 26–40 °C diurnal cyclic temperatures. The adults were tested forWolbachiainfection. Experiments were also carried out rearing the larvae under simulated field conditions in summer (April and June) under sunlight using fully open and half open bowls and also under sunlight and natural shade.

Results

At 36 °C and 40 °C constant temperatures, complete larval mortality was observed. At 30 °C and 26 °C, no larval mortality occurred, butWolbachiadensity was relatively low inwMel infected males compared to control (maintained at 26 ± 1 °C). At diurnal cyclic temperature of 26–40 °C,Wolbachiadensity was reduced in males of both the (Pud) lines, but not in females. At 26–36 °C, reduction inWolbachiadensity was observed inwMel males but not inwAlbB males. At 26–30 °C, no significant reduction inWolbachiadensity was observed withwMel andwAlbB strains. In simulated field conditions (April), under sunlight, the daytime water temperature reached a maximum of 35.7 °C in both full and half open bowls. No larval mortality occurred.Wolbachiafrequency and density was reduced inwMel-infectedAe. aegypti(Pud) males from both type of bowls and in females from full open bowls, and inwAlbB males from half open bowls. In June, rearing of larvae under sunlight, the first-instar larvae experienced a maximum daytime water temperature of > 38 °C that caused complete mortality. No larval mortality was observed in bowls kept under shade (< 32 °C).

Conclusions

Exposure of larvae to higher rearing temperatures in the laboratory and simulated-field conditions reduced the densities ofwMel andwAlbB strains particularly in males, but the impact was more pronounced forwMel strain. The actual effect of heat stress on the stability of these twoWolbachiastrains needs to be tested under natural field conditions.

Graphical Abstract
Myeloid cell-specific deletion of Capns1 prevents macrophage polarization toward the M1 phenotype and reduces interstitial lung disease in the bleomycin model of systemic sclerosis
Authors: Zhang Li , Zheng Dong , Yan Yuemei , Yu Yong , Chen Ruizhen , Li Zheng , Greer Peter A. , Peng Tianqing , Wang Qiang
Published: June 2022

Background

Calpains are a family of calcium-dependent thiol proteases that participate in a wide variety of biological activities. In our recent study, calpain is increased in the sera of scleroderma or systemic sclerosis (SSc). However, the role of calpain in interstitial lung disease (ILD) has not been reported. ILD is a severe complication of SSc, which is the leading cause of death in SSc. The pathogenesis of SSc-related ILD remains incompletely understood. This study investigated the role of myeloid cell calpain in SSc-related ILD.

Methods

A novel line of mice with myeloid cell-specific deletion of Capns1 (Capns1-ko) was created. SSc-related ILD was induced in Capns1-ko mice and their wild-type littermates by injection 0.l mL of bleomycin (0.4 mg/mL) for 4 weeks. In a separate experiment, a pharmacological inhibitor of calpain PD150606 (Biomol, USA, 3 mg/kg/day, i.p.) daily for 30 days was given to mice after bleomycin injection on daily basis. At the end of the experiment, the animals were killed, skin and lung tissues were collected for the following analysis. Inflammation, fibrosis and calpain activity and cytokines were assessed by histological examinations and ELISA, and immunohistochemical analyses, western blot analysis and Flow cytometry analysis.

Results

Calpain activities increased in SSc-mouse lungs. Both deletion of Capns1 and administration of PD150606 attenuated dermal sclerosis as evidenced by a reduction of skin thickness and reduced interstitial fibrosis and inflammation in bleomycin model of SSc mice. These effects of reduced calpain expression or activity were associated with prevention of macrophage polarization toward M1 phenotype and consequent reduced production of pro-inflammatory cytokines including TNF-α, IL-12 and IL-23 in lung tissues of Capns1-ko mice with bleomycin model of SSc. Furthermore, inhibition of calpain correlated with an increase in the protein levels of PI3K and phosphorylated AKT1 in lung tissues of the bleomycin model of SSc mice.

Conclusions

This study for the first time demonstrates that the role of myeloid cell calpain may be promotion of macrophage M1 polarization and pro-inflammatory responses related PI3K/AKT1 signaling. Thus, myeloid cell calpain may be a potential therapeutic target for bleomycin model of SSc-related ILD.