bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum creatinine/cystatin C ratio is a surrogate marker for sarcopenia in patients with idiopathic pulmonary fibrosis
Authors: Fujita Kohei , Ohkubo Hirotsugu , Nakano Akiko , Takeda Norihisa , Fukumitsu Kensuke , Fukuda Satoshi , Kanemitsu Yoshihiro , Uemura Takehiro , Tajiri Tomoko , Maeno Ken , Ito Yutaka , Oguri Tetsuya , Ozawa Yoshiyuki , Murase Takayuki , Niimi Akio
Published: May 2022

Background

The serum creatinine/cystatin C (Cr/CysC) ratio has attracted attention as a marker for sarcopenia, but has not been studied in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to confirm the utility of the serum Cr/CysC ratio in predicting sarcopenia and investigate its clinical relevance.

Methods

This cross-sectional pilot study prospectively enrolled patients with stable IPF. IPF was diagnosed through multidisciplinary discussions according to the 2018 international guidelines, and sarcopenia was diagnosed according to the 2019 consensus report of the Asian Working Group for Sarcopenia. Patient-reported outcomes (PROs) were evaluated using the modified Medical Research Council (mMRC) dyspnea scale, chronic obstructive pulmonary disease assessment test (CAT), and King’s Brief Interstitial Lung Disease (K-BILD) questionnaire. The associations between serum Cr/CysC ratio and the presence of sarcopenia and other clinical parameters, including PROs scores, were examined.

Results

The study enrolled 49 Japanese patients with IPF with a mean age of 73.0 ± 7.7 years and a mean percentage of predicted forced vital capacity of 80.4 ± 15.5%. Sarcopenia was diagnosed in 18 patients (36.7%), and the serum Cr/CysC ratio was 0.86 [0.76–0.94] (median [interquartile range]). The receiver operating characteristic curve analyses for the detection of sarcopenia according to the serum Cr/CysC showed that the area under the curve, optimal cutoff value, specificity, and sensitivity were 0.85, 0.88, 0.65, and 0.94, respectively. Sarcopenia was identified in 13% of patients with a high serum Cr/CysC ratio (≥ 0.88) and 60% of patients with a low serum Cr/CysC ratio (< 0.88) (P < 0.001). Multiple linear regression analysis showed that the serum Cr/CysC ratio was an independent predictive marker of worse PROs evaluated using mMRC (P < 0.05), CAT (P < 0.05), and K-BILD (P < 0.05).

Conclusions

This study showed that the serum Cr/CysC ratio may be a surrogate marker of sarcopenia in patients with IPF. Furthermore, it is important to pay attention to the serum Cr/CysC ratio because a lower serum Cr/CysC ratio is associated with worse PROs. Further studies are required to validate these observations to determine whether the Cr/CysC ratio can be used to detect sarcopenia in patients with IPF.
The effectiveness of weight loss programs for low back pain: a systematic review
Authors: Chen Lu Hsi , Weber Kirsten , Mehrabkhani Saba , Baskaran Sarmina , Abbass Thomas , Macedo Luciana Gazzi
Published: May 2022

Background

Low back pain has been associated with obesity or with being overweight. However, there are no high-quality systematic reviews that have been conducted on the effect of all types of weight loss programs focused on individuals with low back pain. Therefore, the present systematic review aims to evaluate the effectiveness of weight loss programs in reducing back pain and disability or increasing quality of life for individuals experiencing low back pain.

Materials and methods

Searches for relevant studies were conducted on CINAHL, Web of Science, Ovid Medline, Ovid Embase and AMED. Studies were included if they were randomized controlled trials, non-randomized studies of intervention or quasi-experimental designs evaluating a weight loss program for persons with low back pain aimed at decreasing back pain and disability. The Effective Public Health Practice Project (EPHPP) Quality Assessment Tool was used to evaluate individual studies and GRADE was used to summarize the quality of the evidence. The review was prospectively registered; PROSPERO#: CRD42020196099.

Results

Eleven studies (n = 689 participants) including one randomized controlled trial, two non-randomized studies of intervention and eight single-arm studies were included (seven of which evaluated bariatric surgery). There was low-quality evidence that a lifestyle intervention was no better than waitlist for improving back pain and very low-quality evidence from single-arm studies that back pain improved from baseline after bariatric surgery. Most studies included were of poor quality, primarily due to selection bias, uncontrolled confounders, and lack of blinding, limiting the quality of evidence.

Conclusion

There is very low-quality evidence that weight loss programs may improve back pain, disability, and quality of life in patients with LBP, although adherence and maintenance are potential barriers to implementation.
Effects of an integrated supportive program on xerostomia and saliva characteristics in patients with head and neck cancer radiated with a low dose to the major salivary glands: a randomized controlled trial
Authors: Jiang Nan , Zhao Yue , Stensson Malin , Mårtensson Jan
Published: May 2022

Background

Xerostomia and changes in saliva characteristics are common side-effects in patients with head and neck cancer (HNC) undergoing radiotherapy, which negatively impact their oral health. However, there are no consensus standards for intervention to manage these problems. The aim of this study was to determine the effect of an integrated supportive program on xerostomia and saliva characteristics at a 1-year follow-up of patients with HNC radiated with a low dose to the major salivary glands.

Methods

The CONSORT guidelines for a randomized controlled trial were used. Participants with a low overall dose to major salivary glands were randomly allocated to an intervention group (n = 47) or a control group (n = 45). The intervention group received usual care and an integrated supportive program, which included three steps: face-to-face education; face-to-face coaching at 1 month post-radiotherapy; and four telephone coaching sessions at 2, 3, 6, and 9 months post-radiotherapy. The face-to-face education consisted of oral hygiene instruction, oral self-care strategies, facial and tongue muscle exercises, and salivary gland massage. Adherence to the intervention was evaluated using a questionnaire completed during the 9 months follow-up. The control group received usual care. The unstimulated saliva flow rate and xerostomia were assessed in both groups.

Results

A total of 79 participants (40 in the intervention group and 39 in the control group) completed the 12 months follow-up. The intervention group achieved significantly greater relief from xerostomia than the control group after 3 months (intervention group: 35.1 ± 5.9 versus control group: 38.0 ± 5.9, P = 0.027) and 12 months follow-up (intervention group: 18.5 ± 4.1 versus control group: 22.8 ± 4.3, P < 0.001). A higher unstimulated saliva flow rate was observed in the intervention group than the control group at 12 months follow-up (intervention group: 0.16 ± 0.08 versus control group: 0.12 ± 0.07, P = 0.035). Adherence to the intervention was generally good.

Conclusion

This integrated supportive program with good adherence relieved xerostomia and had a positive effect on unstimulated saliva flow rate among patients with HNC radiated with a low dose to the major salivary glands during the 12 months of follow-up.

Trial registration: Chinese Clinical Trial Registry ChiCTR2100051876 (08/10/2021), retrospectively registered.
Success and patient satisfaction of immediately loaded zirconia implants with fixed restorations one year after loading
Authors: Rutkowski Rico , Smeets Ralf , Neuhöffer Leon , Stolzer Carolin , Strick Kilian , Gosau Martin , Sehner Susanne , Volz Karl Ulrich , Henningsen Anders
Published: May 2022

Background

There is limited evidence for the use of zirconium dioxide implants in immediate implant placement as well as for related immediate loading protocols. The aim of this retrospective study was to investigate the survival rate, success and patient satisfaction of immediately placed zirconia implants compared to delayed placed implants.

Methods

The study included 58 partially edentulous patients who were treated between 2013 and 2015 with immediate and delayed transgingival healing zirconium dioxide implants (SDS, Kreuzlingen/ Switzerland). In addition to survival and success rate, marginal bone loss was assessed using radiographs and soft tissue was evaluated using Pink Esthetic Score. Oral health-related quality of life was investigated prospectively using a modified OHIP questionnaire.

Results

The cumulative survival rate of all implants included was 92% with 88% classified as full success. No significant difference was found between the bone levels of immediately and delayed placed and immediately and delayed loaded implants. The mean Pink Esthetic Score after final prosthetic rehabilitation was 12.2/14 points indicating excellent esthetic clinical results. Analysis of the OHIP questionnaire showed a mean value of 0.54/100 points reflecting a high patient satisfaction.

Conclusions

Immediate and delayed placed as well as loaded zirconium dioxide implants showed excellent results regarding implant success and survival in this study. Zirconium dioxide implants may ensure excellent esthetic results and high patient satisfaction.
Effects of mouth breathing on maxillofacial and airway development in children and adolescents with different cervical vertebral maturation stages: a cross-sectional study
Authors: Li Jiahua , Zhao Ziyi , Zheng Leilei , Daraqel Baraa , Liu Jing , Hu Yun
Published: May 2022

Background

To examine the influence of mouth breathing on maxillofacial and airway development in children and adolescents with different cervical vertebral maturation stages.

Methods

Lateral cephalometric radiograph of a total of 120 children and adolescents, 64 girls and 56 boys (7–15 years old), diagnosed with mouth breathing were examined. Maxillofacial hard tissue, soft tissue and airway measurements were obtained using both manual and digital techniques. Independent samples t-test was performed to compare the difference between the measured indexes and the standard values.

Results

As for maxillofacial hard tissue, SNB (CS1–CS5), GoGn (CS1–CS5), ArGoNa (CS1–CS5), ArGo (CS1–CS2) and SNA (CS1–CS2) in mouth breathing children and adolescents were below the standard values (P < 0.05). NGoMe (CS1–CS5), SN-MP (CS1–CS4), SN-PP (CS1–CS4), PP-MP (CS1–CS3) and SN-GoGn (CS1–CS2) in mouth breathing children and adolescents were above the standard values (P < 0.05). As for maxillofacial soft tissue measurements, H angle (CS1–CS5), lower lip length (CS1–CS5), upper lip protrusion (CS1–CS5), upper lip length (CS1–CS4), lower lip protrusion (CS1–CS3), surface Angle (CS2–CS3) and nasolabial angle (CS2) in mouth breathing children and adolescents were above the standard values with statistically significance (P < 0.05). As for airway measurements, PAS (CS1, CS2, CS5) in mouth breathing children and adolescents was above the standard value with statistical significance (P < 0.05).

Conclusions

Mouth breathing had a real effect on maxillofacial and airway development, which differed among mouth breathing children and adolescents with different cervical vertebral maturation.
What is the effectiveness and safety of mirtazapine versus escitalopram in alleviating cancer-associated poly-symptomatology (the MIR-P study)? A mixed-method randomized controlled trial protocol
Authors: Economos Guillaume , Alexandre Marine , Perceau-Chambard Elise , Villeneuve Laurent , Subtil Fabien , Haesebaert Julie , Glehen Olivier
Published: May 2022

Background

Advanced cancer patients often experience multiple symptoms at a same time. This might lead to polypharmacy and increase adverse events representing major threats to the quality of health care, especially in palliative care situations. Mirtazapine, an antidepressant agent, has been suggested as a potential relevant drug to alleviate multiple cancer-related symptoms at a same time.

Therefore, the present study aims to assess the effectiveness of mirtazapine in alleviating multiple symptoms at a same time in advanced cancer patients suffering from a major depressive episode compared to a group receiving escitalopram, another antidepressant agent.

Methods

Multicentre, prospective, randomized, controlled trial in 12 palliative care services in France.

The study will be based on a mixed-method methodology using parallel groups, of oral mirtazapine compared with oral escitalopram, with a 56 day follow-up. The primary outcome will be an improvement of the Global health Status (issued from the EORTC-QLQ-C30) on day 56. 418 participants will be clinically followed-up on day 7 and 56 and will have a telephonic assessment on days 14 and 28. A sub-sample of participants will be invited to take part in semi-structured qualitative interviews at baseline and day 56. For the qualitative part, purposeful sampling will be used.

Discussion

This study will provide evidence for the pharmaceutics management of poly-symptomatology in advanced cancer patients. This could lead to important changes in the management of those patients by using a single molecule to alleviate multiple symptoms at a same time, potentially improving medication adherence, symptoms’ control, and reducing the risk of medications adverse events.

Trial registration

Trial registration: NCT04763135. Registered 18 March 2021.
Determinants of good academic performance among university students in Ethiopia: a cross-sectional study
Authors: Tadese Mesfin , Yeshaneh Alex , Mulu Getaneh Baye
Published: May 2022

Background

Education plays a pivotal role in producing qualified human power that accelerates economic development and solves the real problems of a community. Students are also expected to spend much of their time on their education and need to graduate with good academic results. However, the trend of graduating students is not proportional to the trend of enrolled students and an increasing number of students commit readmission, suggesting that they did not perform well in their academics. Thus, the study aimed to identify the determinants of academic performance among university students in Southern Ethiopia.

Method

Institution-based cross-sectional study was conducted from December 1 to 28, 2020. A total of 659 students were enrolled and data was collected using a self-administered questionnaire. A multistage sampling technique was applied to select study participants. Data were cleaned and entered into Epi-Data version 4.6 and exported to SPSS version 25 software for analysis. Bivariable and multivariable data analysis were computed and ap-value of ≤0.05 was considered statistically significant. Smoking, age, and field of study were significantly associated with academic performance.

Result

Four hundred six (66%) of students had a good academic performance. Students aged between 20 and 24 years (AOR = 0.43, 95% CI = 0.22-0.91), and medical/ health faculty (AOR = 2.46, 95% CI = 1.45-4.20) were significant associates of good academic performance. Students who didn’t smoke cigarettes were three times more likely to score good academic grades compared to those who smoke (AOR = 3.15, 95% CI = 1.21-7.30).

Conclusion

In this study, increased odds of good academic performance were observed among students reported to be non-smokers, adults, and medical/health science students. Reduction or discontinuation of smoking is of high importance for good academic achievement among these target groups. The academic environment in the class may be improved if older students are invited to share their views and particularly their ways of reasoning.
Preparedness for practice of newly qualified dental professionals in Australia - educator, employer, and consumer perspectives
Authors: Mariño Rodrigo , Delany Clare , Manton David , Reid Kate , Satur Julie , Crombie Felicity , Wong Rebecca , McNally Clare , Lopez Diego , Celentano Antonio , Lim Mathew , Morgan Michael
Published: May 2022

Background

Limited data regarding the perspectives of other observers (i.e. those who educate, employ or receive care from) of new graduates’ preparedness to practice is available. The present study aimed to explore perceptions of different observers regarding the preparedness to practice and work readiness of newly qualified dental professionals. This broader range of perspectives is crucial to inform the development of educational programs, including continuing professional development, for newly qualified dental professionals, by clarifying the skills, knowledge and behaviours expected by the dental profession and wider public.

Results

Nineteen individual qualitative interviews were undertaken. Interview participants included clinical demonstrators (n = 9; 2 Oral Health Therapists; 5 Dentists; and 2 Prosthetists), dental course convenors (n = 4), representatives of large employers (n = 2), and consumers (n = 4). According to this diverse group of respondents, dental students receive adequate theoretical and evidence-based information in their formal learning and teaching activities, which prepares them for practice as dental professionals.

There were no specific clinical areas or procedures where preparedness was highlighted as a major concern. Notwithstanding this, specific graduate skills which would benefit from further training and consolidation were identified, including areas where higher levels of experience would be beneficial. Nonetheless, respondents indicated that new graduates were aware of their limitations and had developed self-discipline and ethics that would allow them to identify conditions/situations where they would not have the experience or expertise to provide care safely.

Conclusions

From an observer perspective, dental students appeared to have gained adequate theoretical and evidence-based information in their formal learning and teaching activities to prepared them to commence practicing safely as dental professionals. Areas were identified in which new graduates were underprepared and when transitional support may be required.
Patients’ cancer care perceptions conceptualized through the Cancer Experience Measurement Framework
Authors: Bourque Michaela A. , Loiselle Carmen G.
Published: May 2022

Background

Research on patients’ perceptions of cancer care often documents sub-optimal experiences. Cancer care quality issues include restricted service access, lack of care coordination, gaps in follow-up and “generic” rather than person-centered care. Recent reports underscore that proactively and periodically seeking user feedback is crucial for timely care quality improvement. The present study aimed to analyze and thematically organize a large amount of feedback from patients who had been treated for cancer within the last 6 months.

Methods

Randomly selected participants (N = 3,278) from 3 University-affiliated cancer centres in Montreal, Quebec, Canada completed the Ambulatory Oncology Patient Satisfaction Survey (AOPSS) and an open-ended question on their perceptions of the care they received. 692 participants responded to the latter. Guided by the Cancer Experience Measurement Framework (CEMF), their feedback was analyzed using a qualitative thematic approach.

Results

Cancer care perceptions included sub-themes of care access and coordination, continuity/transition, and perceived appropriateness/personalisation of care.

The most salient theme was captured by care access and coordination with 284 comments (44%) directly addressing these issues. The ways in which health care services were structured including setting, schedule, and location were often raised as cause for concerns. Issues surrounding cancer information/education, emotional support, and physical comfort were frequently reported as unmet needs. In addition, limited access to cancer services led patients to seek alternatives such as going to emergency departments and/or private care.

Conclusions

These findings are timely as they show that most patients are well aware of quality issues in cancer care and are willing to report candidly on these. Patient feedback also underscore the importance for cancer care institutions to periodically gather patient-reported data so that systems can re-calibrate their service offerings according to these data. Ultimately, patient reports will translate into enhanced quality, personalization, and safer cancer care provision.
What is needed for continuity of care and how can we achieve it? – Perceptions among multiprofessionals on the chronic care trajectory
Authors: Ljungholm Linda , Edin-Liljegren Anette , Ekstedt Mirjam , Klinga Charlotte
Published: May 2022

Background

Continuity of care (CoC) implies delivery of services in a coherent, logical and timely fashion. Continuity is conceptualized as multidimensional, encompassing three specific domains – relational, management and informational continuity – with emphasis placed on their interrelations, i.e., how they affect and are affected by each other. This study sought to investigate professionals’ perceptions of the prerequisites of CoC within and between organizations and how CoC can be realized for people with complex care needs.

Methods

This study had a qualitative design using individual, paired and focus group interviews with a purposeful sample of professionals involved in the chain of care for patients with chronic conditions across healthcare and social care services from three different geographical areas in Sweden, covering both urban and rural areas. Transcripts from interviews with 34 informants were analysed using conventional content analysis.

Results

CoC was found to be dependent on professional and cross-disciplinary cooperation at the micro, meso and macro system levels. Continuity is dependent on long-term and person-centred relationships (micro level), dynamic stability in organizational structures (meso level) and joint responsibility for cohesive care and enabling of uniform solutions for knowledge and information exchange (macro level).

Conclusions

Achieving CoC that creates coherent and long-term person-centred care requires knowledge- and information-sharing that transcends disciplinary and organizational boundaries. Collaborative accountability is needed both horizontally and vertically across micro, meso and macro system levels, rather than a focus on personal responsibility and relationships at the micro level.
Physicians’ perspectives and future vision on disability assessments by phone during the COVID-19 pandemic: a cross-sectional survey
Authors: Baart Nadia , Hoving Jan Lucas , Donker-Cools Birgit Helena Petra Maria
Published: May 2022

Background

Physicians, who perform disability assessments for the Dutch Social Security Institute, were urged to conduct phone consultations from their homes to prevent the spread of COVID-19. The purpose of the study was to evaluate the perspectives of physicians regarding phone consultations during the COVID-19 pandemic. Additionally, to explore physicians’ views on a more widespread future use of phone consultations in the context of work disability assessments.

Methods

An electronic survey conducted from June to August 2020 included 41 statements categorized into themes previously identified in both the literature on physicians’ phone consultations and emerging from daily practice. All 1081 physicians working at the Dutch Social Security Institute were invited by e-mail to participate in the survey. Participants indicated on a 5-point Likert scale whether they strongly disagreed, disagreed, neither agreed nor disagreed, agreed or strongly agreed with the statements. The collected data were analysed using descriptive statistics.

Results

In general, physicians had become accustomed to perform phone consultations. Negative experiences included difficulties in getting an impression of patients and assessing patients’ functional limitations. About half of physicians found that phone consultations took more effort, 61% asked more questions due to no direct patient observations. According to 67%, it is mostly necessary to perform an in-person consultation to adequately assess functional limitations of a patient with persistent medically unexplained physical symptoms. A great majority did not prefer telephone consultations to in-person consultations. However, more than half of physicians perceive a greater preference for phone consultations in the future than previously. 56% thought that replacement of in-person consultations with phone consultations in the future might lead to more complaints.

Conclusions

Perspectives and future views varied among physicians performing disability assessments by phone. A majority of physicians experienced difficulties with different aspects of the assessment. Despite these difficulties, most physicians support to continue the wider use of phone consultations. To improve remote disability assessments it is required to gain more insights into conditions under which a phone assessment can be as diligent as an in-person assessment.
Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: a systematic review and meta-analysis
Authors: Zeng Baoqi , Gao Le , Zhou Qingxin , Yu Kai , Sun Feng
Published: May 2022

Background

It was urgent and necessary to synthesize the evidence for vaccine effectiveness (VE) against SARS-CoV-2 variants of concern (VOC). We conducted a systematic review and meta-analysis to provide a comprehensive overview of the effectiveness profile of COVID-19 vaccines against VOC.

Methods

Published randomized controlled trials (RCTs), cohort studies, and case-control studies that evaluated the VE against VOC (Alpha, Beta, Gamma, Delta, or Omicron) were searched until 4 March 2022. Pooled estimates and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis. VE was defined as (1-estimate).

Results

Eleven RCTs (161,388 participants), 20 cohort studies (52,782,321 participants), and 26 case-control studies (2,584,732 cases) were included. Eleven COVID-19 vaccines (mRNA-1273, BNT162b2, ChAdOx1, Ad26.COV2.S, NVX-CoV2373, BBV152, CoronaVac, BBIBP-CorV, SCB-2019, CVnCoV, and HB02) were included in this analysis. Full vaccination was effective against Alpha, Beta, Gamma, Delta, and Omicron variants, with VE of 88.0% (95% CI, 83.0–91.5), 73.0% (95% CI, 64.3–79.5), 63.0% (95% CI, 47.9–73.7), 77.8% (95% CI, 72.7–82.0), and 55.9% (95% CI, 40.9–67.0), respectively. Booster vaccination was more effective against Delta and Omicron variants, with VE of 95.5% (95% CI, 94.2–96.5) and 80.8% (95% CI, 58.6–91.1), respectively. mRNA vaccines (mRNA-1273/BNT162b2) seemed to have higher VE against VOC over others; significant interactions (pinteraction < 0.10) were observed between VE and vaccine type (mRNA vaccines vs. not mRNA vaccines).

Conclusions

Full vaccination of COVID-19 vaccines is highly effective against Alpha variant, and moderate effective against Beta, Gamma, and Delta variants. Booster vaccination is more effective against Delta and Omicron variants. mRNA vaccines seem to have higher VE against Alpha, Beta, Gamma, and Delta variants over others.
Time trends in social contacts of individuals according to comorbidity and vaccination status, before and during the COVID-19 pandemic
Authors: Godbout Aurélie , Drolet Mélanie , Mondor Myrto , Simard Marc , Sauvageau Chantal , De Serres Gaston , Brisson Marc
Published: May 2022

Background

As we are confronted with more transmissible/severe variants with immune escape and the waning of vaccine efficacy, it is particularly relevant to understand how the social contacts of individuals at greater risk of COVID-19 complications evolved over time. We described time trends in social contacts of individuals according to comorbidity and vaccination status before and during the first three waves of the COVID-19 pandemic in Quebec, Canada.

Methods

We used data from CONNECT, a repeated cross-sectional population-based survey of social contacts conducted before (2018/2019) and during the pandemic (April 2020 to July 2021). We recruited non-institutionalized adults from Quebec, Canada, by random digit dialling. We used a self-administered web-based questionnaire to measure the number of social contacts of participants (two-way conversation at a distance ≤2 m or a physical contact, irrespective of masking). We compared the mean number of contacts/day according to the comorbidity status of participants (pre-existing medical conditions with symptoms/medication in the past 12 months) and 1-dose vaccination status during the third wave. All analyses were performed using weighted generalized linear models with a Poisson distribution and robust variance.

Results

A total of 1441 and 5185 participants with and without comorbidities, respectively, were included in the analyses. Contacts significantly decreased from a mean of 6.1 (95%CI 4.9–7.3) before the pandemic to 3.2 (95%CI 2.5–3.9) during the first wave among individuals with comorbidities and from 8.1 (95%CI 7.3–9.0) to 2.7 (95%CI 2.2–3.2) among individuals without comorbidities. Individuals with comorbidities maintained fewer contacts than those without comorbidities in the second wave, with a significant difference before the Christmas 2020/2021 holidays (2.9 (95%CI 2.5–3.2) vs 3.9 (95%CI 3.5–4.3); P<0.001). During the third wave, contacts were similar for individuals with (4.1, 95%CI 3.4–4.7) and without comorbidities (4.5, 95%CI 4.1–4.9; P=0.27). This could be partly explained by individuals with comorbidities vaccinated with their first dose who increased their contacts to the level of those without comorbidities.

Conclusions

It will be important to closely monitor COVID-19-related outcomes and social contacts by comorbidity and vaccination status to inform targeted or population-based interventions (e.g., booster doses of the vaccine).
Compartmentalization and transporter engineering strategies for terpenoid synthesis
Authors: Jin Ke , Xia Hongzhi , Liu Yanfeng , Li Jianghua , Du Guocheng , Lv Xueqin , Liu Long
Published: May 2022

Microbial cell factories for terpenoid synthesis form a less expensive and more environment-friendly approach than chemical synthesis and extraction, and are thus being regarded as mainstream research recently. Organelle compartmentalization for terpenoid synthesis has received much attention from researchers owing to the diverse physiochemical characteristics of organelles. In this review, we first systematically summarized various compartmentalization strategies utilized in terpenoid production, mainly plant terpenoids, which can provide catalytic reactions with sufficient intermediates and a suitable environment, while bypassing competing metabolic pathways. In addition, because of the limited storage capacity of cells, strategies used for the expansion of specific organelle membranes were discussed. Next, transporter engineering strategies to overcome the cytotoxic effects of terpenoid accumulation were analyzed. Finally, we discussed the future perspectives of compartmentalization and transporter engineering strategies, with the hope of providing theoretical guidance for designing and constructing cell factories for the purpose of terpenoid production.
Brain-targeted heptapeptide-loaded exosomes attenuated ischemia–reperfusion injury by promoting the transfer of healthy mitochondria from astrocytes to neurons
Authors: Liu Wei , Su Chang , Qi Yao , Liang Jia , Zhao Liang , Shi Yijie
Published: May 2022

Background

The exchange of mitochondria reportedly plays an important role in cell–cell communication in the central nervous system (CNS). The transfer of fragmented and dysfunctional astrocytic mitochondria into neurons and subsequent mitochondrial fusion often cause serious neuronal damage and cerebral ischaemic injury.

Methods

In this study, we prepared macrophage-derived exosomes laden with heptapeptide (Hep) as a dynamin-related protein-1 (Drp1)–fission 1 (Fis1) peptide inhibitor P110 to alleviate cerebral ischemia–reperfusion injury by reducing mitochondrial Drp1/Fis1 interaction-mediated astrocytic mitochondrial disorder and promoting the transfer of astrocyte-derived healthy mitochondria into neurons.

Results

The results demonstrated that Hep-loaded macrophage-derived exosomes (EXO-Hep) reduced mitochondrial damage in astrocytes by inhibiting the Drp1/Fis1 interaction after ischemia–reperfusion, ensuring the release of heathy astrocytic mitochondria and their subsequent transmission to neurons, alleviating mitochondria-mediated neuronal damage.

Conclusion

EXO-Hep significantly mitigated ischemic injury in a model of transient middle cerebral artery occlusion (tMCAO) by reducing the infarct area and improving neurological performance during the process of cerebral ischemia–reperfusion.

Graphical Abstract
Nursing engagement in research priorities focused on health systems and services in Latin America countries
Authors: Hughes Tonda L. , George Maureen , Shah Ruby , Dias Bruna Moreno , Dohrn Jennifer E. , De Bortoli Cassiani Silvia Helena
Published: May 2022

Background

A strong nursing research agenda in Latin America is fundamental to universal health coverage. Nursing science can make important contributions to the health of Latin American people through knowledge generation that directly informs nursing practice, professional education, and health policy.

Methods

We used a cross-sectional survey design to assess nursing involvement in health systems and services research in Latin America in five priority areas: Policies and education related to nursing human resources; Structure, organization and dynamics of health systems and services; Science, technology, innovation, and information systems in public health; Health policies, governance, and social control; and Social studies in the health field.

Results

Nursing and midwifery participants (N = 856) from Latin American countries completed the survey. Respondents who reported conducting research focused primarily on Policies and Education related to Nursing Human Resources and Structure, Organization, and Dynamics of Health Systems and Services. Across the five priority areas, more nurses reported using research findings and/or being aware of research than conducting research.

Conclusions

Survey results indicate that nursing research in Latin America is currently disproportionately focused on nursing education and practice. More research focused on information technology, nurse’s impact on public health, and the threats posed by nurse migration is needed to better address health needs of Latin American populations.
Plant-derived extracellular vesicles: a novel nanomedicine approach with advantages and challenges
Authors: Nemati Mohadeseh , Singh Bipin , Mir Rakeeb Ahmad , Nemati Mahdieh , Babaei Azadeh , Ahmadi Mahdi , Rasmi Yousef , Golezani Afsaneh Gholinejad , Rezaie Jafar
Published: May 2022

Background

Many eukaryote cells produce membrane-enclosed extracellular vesicles (EVs) to establish cell-to-cell communication. Plant-derived EVs (P-EVs) contain proteins, RNAs, lipids, and other metabolites that can be isolated from the juice, the flesh, and roots of many species.

Methods

In the present review study, we studied numerous articles over the past two decades published on the role of P-EVs in plant physiology as well as on the application of these vesicles in different diseases.

Results

Different types of EVs have been identified in plants that have multiple functions including reorganization of cell structure, development, facilitating crosstalk between plants and fungi, plant immunity, defense against pathogens. Purified from several edible species, these EVs are more biocompatible, biodegradable, and extremely available from many plants, making them useful for cell-free therapy. Emerging evidence of clinical and preclinical studies suggest that P-EVs have numerous benefits over conventional synthetic carriers, opening novel frontiers for the novel drug-delivery system. Exciting new opportunities, including designing drug-loaded P-EVs to improve the drug-delivery systems, are already being examined, however clinical translation of P-EVs-based therapies faces challenges.

Conclusion

P-EVs hold great promise for clinical application in the treatment of different diseases. In addition, despite enthusiastic results, further scrutiny should focus on unravelling the detailed mechanism behind P-EVs biogenesis and trafficking as well as their therapeutic applications.
Association between physical activity and infertility: a comprehensive systematic review and meta-analysis
Authors: Xie Fangfang , You Yanli , Guan Chong , Gu Yuanjia , Yao Fei , Xu Jiatuo
Published: May 2022

Background

Physical activity (PA) may protect against infertility by modulating the hypothalamic-pituitary–gonadal axis, thereby reducing gonadotropin levels, elevating immune function, and inhibiting inflammation and circulating sex hormones. However, whether PA reduces the risk of infertility remains largely unknown. We therefore conducted a systematic review and meta-analysis to determine the preventive effects of PA on infertility.

Methods

We searched PubMed, Cochrane Library, EMBASE, and CINAHL databases to retrieve published epidemiologic studies on the relationship between PA and infertility. Following the PRISMA guidelines, we selected English literature publishedprior to 11 April 2022, and assessed study quality using the Newcastle–Ottawa Scale. Our protocol, including the full methods employed for this review, is available on PROSPERO (ID = CRD42020143344).

Results

Six cohort studies and four case–control studies based on 708,965 subjects and 12,580 cases were eventually screened and retained. High levels of PA were shown to reduced risk of infertility relative to low levels (cumulative relative risk [RR] = 0.59, with a 95% confidence interval CI 0.49–0.71), and we reported results for cohort studies (RR = 0.63, 95% CI 0.50–0.79) and case–control studies (RR = 0.49, 95% CI 0.35–0.67). Our findings were comparable for men (RR = 0.65, 95% CI 0.41–1.04) and women (RR = 0.56, 95% CI 0.47–0.66). The meta-analysis of six risk estimates from five studies of low, moderate, and high PA levels showed that moderate PA may also reduce the risk of infertility compared with low PA (RR = 0.54, 95% CI 0.38–0.77). However, high PA also appeared to slightly augment the risk of infertility compared with moderate PA (RR = 1.31, 95% CI 1.08–1.59).

Conclusions

This present systematic review comprehensively reflected an inverse relationship between different levels of PA and infertility, and our meta-analysis showed that a moderate-to-high PA level significantly reduced the overall risk of infertility, and that this level of PA activity was a common protective factor. In addition, limited evidence suggested that compliance with international PA guidelines would greatly lower the risk of infertility (RR = 0.58, 95% CI 0.45–0.74; I2 = 0.0%). Future studies, however, need to be executed to further determine the frequency, optimal dosage, and duration required to effectively attenuate the risk of infertility.
Lymphocytes in tumor-draining lymph nodes co-cultured with autologous tumor cells for adoptive cell therapy
Authors: Okamura Kazumi , Nagayama Satoshi , Tate Tomohiro , Chan Hiu Ting , Kiyotani Kazuma , Nakamura Yusuke
Published: May 2022

Background

Tumor-draining lymph nodes (TDLNs) are primary sites, where anti-tumor lymphocytes are primed to tumor-specific antigens and play pivotal roles in immune responses against tumors. Although adoptive cell therapy (ACT) using lymphocytes isolated from TDLNs were reported, characterization of immune activity of lymphocytes in TDLNs to tumor cells was not comprehensively performed. Here, we demonstrate TDLNs to have very high potential as cell sources for immunotherapy.

Methods

Lymphocytes from TDLNs resected during surgical operation were cultured with autologous-tumor cells for 2 weeks and evaluated tumor-reactivity by IFNγ ELISPOT assay. We investigated the commonality of T cell receptor (TCR) clonotypes expanded by the co-culture with tumor cells with those of tumor infiltrating lymphocytes (TILs).

Results

We found that that TCR clonotypes of PD-1-expressing CD8+ T cells in lymph nodes commonly shared with those of TILs in primary tumors and lymphocytes having tumor-reactivity and TCR clonotypes shared with TILs could be induced from non-metastatic lymph nodes when they were co-cultured with autologous tumor cells.

Conclusion

Our results imply that tumor-reactive effector T cells were present even in pathologically non-metastatic lymph nodes and could be expanded in vitro in the presence of autologous tumor cells and possibly be applied for ACT.
Association between immunoglobulin A and depression in Chinese older adults: findings from a cross-sectional study
Authors: Sun Zhigao , Lin Jieqiong , Zhang Yujie , Yao Yao , Huang Zhenjun , Zhao Yali , Zhang Pei , Fu Shihui
Published: May 2022

Background

Depression is considered to be an immune-related disease; however, previous studies have focused on inflammatory factors, and there is no conclusive conclusion on the relationships between immunoglobulins and depression. Therefore, the objective of this cross-sectional study was to evaluate the associations between immunoglobulins and depressive symptoms in Chinese older adults.

Results

The China Hainan Centenarian Cohort Study (CHCCS) provides a significant population-based sample of older adults in Hainan, China. A total of 1547 older adults were included in this study. A baseline survey was conducted using a structured questionnaire. Blood samples were obtained following standard procedures. The Geriatric Depression Scale (GDS-15) was used to evaluate depressive symptoms of the participants. This sample of older adults had a median age of 94.75 (range: 80–116) years, and the proportion of women was 72.07%. The prevalence of older adults with depressive symptoms was 20.36% (315 older adults). After adjusting for all covariates, we found that immunoglobulin A levels were positively associated with depression. The adjusted reliability of the association between immunoglobulin A and depression was 0.106 (beta) and 1.083 (odds ratio) (P < 0.05 for both).

Conclusions

The present study provides epidemiological evidence that depression has significant associations with immunoglobulin A levels in older adults. Further research should be conducted on the effects of regulating immunoglobulin A to improve depressive symptoms.
Shortcutting the diagnostic odyssey: the multidisciplinary Program for Undiagnosed Rare Diseases in adults (UD-PrOZA)
Authors: Schuermans Nika , Hemelsoet Dimitri , Terryn Wim , Steyaert Sanne , Van Coster Rudy , Coucke Paul J. , Steyaert Wouter , Callewaert Bert , Bogaert Elke , Verloo Patrick , Vanlander Arnaud V. , Debackere Elke , Ghijsels Jody , LeBlanc Pontus , Verdin Hannah , Naesens Leslie , Haerynck Filomeen , Callens Steven , Dermaut Bart , Poppe Bruce ,   for UD-PrOZA, De Bleecker Jan , Santens Patrick , Boon Paul , Laureys Guy , Kerre Tessa
Published: May 2022

Background

In order to facilitate the diagnostic process for adult patients suffering from a rare disease, the Undiagnosed Disease Program (UD-PrOZA) was founded in 2015 at the Ghent University Hospital in Belgium. In this study we report the five-year results of our multidisciplinary approach in rare disease diagnostics.

Methods

Patients referred by a healthcare provider, in which an underlying rare disease is likely, qualify for a UD-PrOZA evaluation. UD-PrOZA uses a multidisciplinary clinical approach combined with state-of-the-art genomic technologies in close collaboration with research facilities to diagnose patients.

Results

Between 2015 and 2020, 692 patients (94% adults) were referred of which 329 (48%) were accepted for evaluation. In 18% (60 of 329) of the cases a definite diagnosis was made. 88% (53 of 60) of the established diagnoses had a genetic origin. 65% (39 of 60) of the genetic diagnoses were made through whole exome sequencing (WES). The mean time interval between symptom-onset and diagnosis was 19 years. Key observations included novel genotype–phenotype correlations, new variants in known disease genes and the identification of three new disease genes. In 13% (7 of 53), identifying the molecular cause was associated with therapeutic recommendations and in 88% (53 of 60), gene specific genetic counseling was made possible. Actionable secondary findings were reported in 7% (12 of 177) of the patients in which WES was performed.

Conclusion

UD-PrOZA offers an innovative interdisciplinary platform to diagnose rare diseases in adults with previously unexplained medical problems and to facilitate translational research.
Paraventricular hypothalamic vasopressin neurons induce self-grooming in mice
Authors: Islam Md Tarikul , Maejima Takashi , Matsui Ayako , Mieda Michihiro
Published: May 2022

Self-grooming plays an essential role in hygiene maintenance, thermoregulation, and stress response. However, the neural populations involved in self-grooming remain largely unknown. The paraventricular hypothalamic nucleus (PVH) has been implicated in the regulation of self-grooming. Arginine vasopressin-producing neurons are among the major neuronal populations in the PVH (PVHAVP), which play important roles in water homeostasis, blood pressure regulation, feeding, and stress response. Here, we report the critical role of PVHAVP neurons in the induction of self-grooming. Optogenetic activation of PVHAVP neurons immediately induced self-grooming in freely moving mice. Chemogenetic activation of these neurons also increased time spent self-grooming. In contrast, their chemogenetic inhibition significantly reduced naturally occurring self-grooming, suggesting that PVHAVP-induced grooming has physiological relevance. Notably, optogenetic activation of PVHAVP neurons triggered self-grooming over other adaptive behaviors, such as voracious feeding induced by fasting and social interaction with female mice. Thus, our study proposes the novel role of PVHAVP neurons in regulating self-grooming behavior and, consequently, hygiene maintenance and stress response. Furthermore, uncontrolled activation of these neurons may be potentially relevant to diseases characterized by compulsive behaviors and impaired social interaction, such as autism, obsessive–compulsive disorder, and anorexia nervosa.
Statewide trends and factors associated with genetic testing for hereditary cancer risk in Arkansas 2013–2018
Authors: Acharya Mahip , Zorn Kristin K. , Simonson Melinda E. , Bimali Milan , Moore Gary W. , Peng Cheng , Martin Bradley C.
Published: May 2022

Background

Early identification of hereditary cancer risk would save lives, but genetic testing (GT) has been inadequate. We assessed i) trends for hereditary breast and ovarian cancer (HBOC), Lynch syndrome, and other GT and ii) factors associated with receipt of GT.

Methods

We used data from the Arkansas All-Payer Claims Database from January 2013 through June 2018 (commercial, Medicaid), December 2017 (state employee), or December 2016 (Medicare) and identified enrollees with ≥1 month of enrollment. Using Current Procedural Terminology (CPT-4) codes, rates for GT were calculated per 100,000 person-quarters and time series regressions estimated. Second, GT and covariate information for enrollees with 24 months of continuous enrollment were used to estimate separate logistic regression models for each GT category.

Results

Among 2,520,575 unique enrollees, HBOC testing rates were 2.2 (Medicaid), 22.0 (commercial), 40.4 (state employee), and 13.1(Medicare) per 100,000 person-quarters and increased linearly across all plans. Older age (OR=1.24; 95%CI 1.20 – 1.28), female sex (OR=18.91; 95%CI 13.01 – 28.86), higher comorbidity burden (OR=1.08; 95%CI 1.05 – 1.12), mental disorders (OR=1.53; 95%CI 1.15 – 2.00), and state employee coverage (OR=1.65; 95%CI 1.37 – 1.97) were positively associated with HBOC testing. Less than 1 of 10,000 enrollees received Lynch syndrome testing, while < 5 of 10,000 received HBOC testing.

Conclusion

GT rates for hereditary cancer syndromes have increased in Arkansas but remain low. Receipt of GT was explained with high discrimination by sex and plan type.

Impact

Expansion of GT for hereditary cancer risk in Arkansas is needed to identify high-risk individuals who could benefit from risk-reduction strategies.