bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in medical students´ and anesthesia technician trainees´ attitudes towards interprofessionality – experience from an interprofessional simulation-based course
Authors: Becker Veronika , Jedlicska Nana , Scheide Laura , Nest Alexandra , Kratzer Stephan , Hinzmann Dominik , Wijnen-Meijer Marjo , Berberat Pascal O. , Haseneder Rainer
Published: April 2022

Background

Interprofessional simulation based education (IPSBE) programs positively impact participants' attitudes towards interprofessional collaboration and learning. However, the extent to which students in different health professions benefit and the underlying reasons for this are subject of ongoing debate.

Methods

We developed a 14-h IPSBE course with scenarios of critical incidents or emergency cases. Participants were final year medical students (FYMS) and final year anesthesia technician trainees (FYATT). To assess attitudes towards interprofessionalism, the University of the West of England Interprofessional Questionnaire was administrated before and after the course. Using focus group illustration maps, qualitative data were obtained from a subcohort of the participants (n = 15).

Results

After the course, self-assessment of communication and teamwork skills, attitudes towards interprofessional interactions and relationships showed comparative improvement in both professions. Attitudes towards interprofessional learning improved only in FYMS. Qualitative data revealed teamwork, communication, hierarchy and the perception of one’s own and other health profession as main topics that might underlie the changes in participants’ attitudes. An important factor was that participants got to know each other during the course and understood each other's tasks.

Conclusions

Since adequate communication and teamwork skills and positive attitudes towards interprofessionality account to effective interprofessional collaboration, our data support intensifying IPSBE in undergraduate health care education.
Nurse staffing levels within acute care: results of a national day of care survey
Authors: Hegarty Hannah , Knight Thomas , Atkin Catherine , Kelly Tash , Subbe Chris , Lasserson Daniel , Holland Mark
Published: April 2022

Introduction

The relationship between nurse staffing levels and patient safety is well recognised. Inadequate provision of nursing staff is associated with increased medical error, as well as higher morbidity and mortality. Defining what constitutes safe nurse staffing levels is complex. A range of guidance and planning tools are available to inform staffing decisions. The Society for Acute Medicine (SAM) recommend a ‘nurse-to-bed‘ratio of greater than 1:6. Whether this standard accurately reflects the pattern and intensity of work on the Acute Medical Unit (AMU) is unclear.

Methods

Nurse staffing levels in AMUs were explored using the Society for Acute Medicine Benchmarking Audit 2019 (SAMBA19). Data from 122 acute hospitals were analysed. Nurse-to-bed ratios were calculated and compared. Estimates of the total nursing time available within the acute care system were compared to estimates of the time required to perform nursing activities.

Results

The total number of AMU beds across all 122 units was 4997. The mean daytime nurse-to-bed ratio was 1:4.3 and the mean night time nurse-to-bed ratio was 1:5.2. The SAM standard of a nurse to bed ratio of greater than 1:6 was achieved in 99 units (81.9%) during daytime hours and achieved by 74 units (60.6%) at night.

The estimated time required to deliver direct clinical care was 35,698 h. A deficit of 4128 h (11.5% of time required) was estimated, representing the time difference between the total number of nursing hours available with current staffing and the estimated time needed for direct clinical care across all participating units.

Conclusion

This UK-wide study suggests a significant proportion of AMUs do not meet the recommenced SAM staffing levels, particularly at night. A difference was observed between the total number of nursing hours within the acute care system and the estimated time required to perform direct nursing activities. This suggests a workforce shortage of nurses within acute care at the system level.
Pyruvate kinase, a metabolic sensor powering glycolysis, drives the metabolic control of DNA replication
Authors: Horemans Steff , Pitoulias Matthaios , Holland Alexandria , Pateau Emilie , Lechaplais Christophe , Ekaterina Dariy , Perret Alain , Soultanas Panos , Janniere Laurent
Published: April 2022

Background

In all living organisms, DNA replication is exquisitely regulated in a wide range of growth conditions to achieve timely and accurate genome duplication prior to cell division. Failures in this regulation cause DNA damage with potentially disastrous consequences for cell viability and human health, including cancer. To cope with these threats, cells tightly control replication initiation using well-known mechanisms. They also couple DNA synthesis to nutrient richness and growth rate through a poorly understood process thought to involve central carbon metabolism. One such process may involve the cross-species conserved pyruvate kinase (PykA) which catalyzes the last reaction of glycolysis. Here we have investigated the role of PykA in regulating DNA replication in the model system Bacillus subtilis.

Results

On analysing mutants of the catalytic (Cat) and C-terminal (PEPut) domains of B. subtilis PykA we found replication phenotypes in conditions where PykA is dispensable for growth. These phenotypes are independent from the effect of mutations on PykA catalytic activity and are not associated with significant changes in the metabolome. PEPut operates as a nutrient-dependent inhibitor of initiation while Cat acts as a stimulator of replication fork speed. Disruption of either PEPut or Cat replication function dramatically impacted the cell cycle and replication timing even in cells fully proficient in known replication control functions. In vitro, PykA modulates activities of enzymes essential for replication initiation and elongation via functional interactions. Additional experiments showed that PEPut regulates PykA activity and that Cat and PEPut determinants important for PykA catalytic activity regulation are also important for PykA-driven replication functions.

Conclusions

We infer from our findings that PykA typifies a new family of cross-species replication control regulators that drive the metabolic control of replication through a mechanism involving regulatory determinants of PykA catalytic activity. As disruption of PykA replication functions causes dramatic replication defects, we suggest that dysfunctions in this new family of universal replication regulators may pave the path to genetic instability and carcinogenesis.
Difference in cardiac remodeling between female athletes and pregnant women: a case control study
Authors: Toncelli Loira , Pasquini Lucia , Masini Giulia , Orlandi Melissa , Paci Gabriele , Mecacci Federico , Pedrizzetti Gianni , Galanti Giorgio
Published: April 2022

Objectives

The aim of this study was to detect possible differences in reversible cardiac remodeling occurring in sport training and twin pregnancy. Background: cardiac remodeling occurs in athletes and pregnant women due to training and fetal requirements, respectively. These changes could be apparently similar.

Methods

21 female elite athletes (23.2 ± 5.3 years), 25 women with twin pregnancies (35.4 ± 5.7 years) and 25 healthy competitive female athletes (controls), age-matched with pregnant women (34.9 ± 7.9 years), were enrolled. This latter group was included to minimize the effect of age on cardiac remodeling. All women evaluated through anamnestic collection, physical examination, 12 leads ECG, standard echocardiogram and strain analysis. Sphericity (SI) and apical conicity (ACI) indexes were also calculated.

Results

Pregnant women showed higher LA dimension (p < 0.001) compared to both groups of athletes. LV e RV GLS were significantly different in pregnant women compared to female athletes (p = 0.02 and 0.03, respectively). RV GLS was also different between pregnant women and controls (p = 0.02). Pregnant women showed significantly higher S′ wave compared to female athletes (p = 0.02) but not controls. Parameters of diastolic function were significantly higher in athletes (p = 0.08 for IVRT and p < 0.001 for E/A,). SI was lower in athletes in both diastole (p = 0.01) and systole (p < 0.001), while ACIs was lower in pregnant women (p = 0.04).

Conclusions

Cardiac remodeling of athletes and pregnant women could be similar at first sight but different in LV shape and in GLS, highlighting a profound difference in longitudinal deformation between athletes and pregnant women. This difference seems not to be related with age. These findings suggest that an initial maternal cardiovascular maladaptation could occur in the third trimester of twin pregnancies.
Microparticles: biogenesis, characteristics and intervention therapy for cancers in preclinical and clinical research
Authors: Hu Yan , Sun Yajie , Wan Chao , Dai Xiaomeng , Wu Shuhui , Lo Pui-Chi , Huang Jing , Lovell Jonathan F. , Jin Honglin , Yang Kunyu
Published: April 2022

Extracellular vesicles (EVs), spherical biological vesicles, mainly contain nucleic acids, proteins, lipids and metabolites for biological information transfer between cells. Microparticles (MPs), a subtype of EVs, directly emerge from plasma membranes, and have gained interest in recent years. Specific cell stimulation conditions, such as ultraviolet and X-rays irradiation, can induce the release of MPs, which are endowed with unique antitumor functionalities, either for therapeutic vaccines or as direct antitumor agents. Moreover, the size of MPs (100–1000 nm) and their spherical structures surrounded by a lipid bilayer membrane allow MPs to function as delivery vectors for bioactive antitumor compounds, with favorable phamacokinetic behavior, immunostimulatory activity and biological function, without inherent carrier-specific toxic side effects. In this review, the mechanisms underlying MP biogenesis, factors that influence MP production, properties of MP membranes, size, composition and isolation methods of MPs are discussed. Additionally, the applications and mechanisms of action of MPs, as well as the main hurdles for their applications in cancer management, are introduced.

Graphical Abstract
Lymph node-targeted neoantigen nanovaccines potentiate anti-tumor immune responses of post-surgical melanoma
Authors: Chu Yanhong , Qian Lingyu , Ke Yaohua , Feng Xiaoyu , Chen Xinjie , Liu Fangcen , Yu Lixia , Zhang Lianru , Tao Yaping , Xu Rui , Wei Jia , Liu Baorui , Liu Qin
Published: April 2022

Background

Neoantigens are considered ideal targets for immunotherapy, especially tumor vaccine, because of their strong specificity and immunogenicity. Here, we developed a neoantigen nanovaccine used liposomes with lymph-node targeting characteristic.

Methods

Our nanovaccine was composed of neoantigens, an amphiphilic liposome and an adjuvant Montanide™ ISA 51. Small animal imaging system and immunofluorescence staining were used to identify the distribution of nanovaccines. A subcutaneous-tumor-resection mouse model of melanoma was established to evaluate the anti-tumor efficacy. Flow cytometry was performed to assay the immune responses initiated by nanovaccines.

Results

Nanovaccines could traffic to lymph nodes, be uptaken by CD11c+ DCs and promote DCs maturity. After the treatment of our neoantigen nanovaccines, the average recurrence time was extended from 11 to 16 days and the median survival time was even prolonged 7.5 days relative to the control group (NS group). Nanovaccines increased neoantigen-specific T cells to 10-fold of free vaccines, and upregulated Th1 cytokines, such as IFN-γ and TNF-α. The anti-tumor activity of spleen lymphocytes in the nanovaccine group was significantly stronger than that of other groups. However, some immune-inhibitory cells or molecules in tumor microenvironment have been detected upregulated under the immune pressure of neoantigen nanovaccines, such as Tregs and PD-L1. The efficacy of the neoantigen nanovaccine combined with anti-PD1 antibody or Treg inhibiting peptide P60 was better than that of the single treatment.

Conclusions

We developed a general vaccine strategy, triggering specific T cell responses, and provided feasible combination strategies for better anti-tumor efficacy.

Graphical abstract
Diversity and ethnomycological importance of mushrooms from Western Himalayas, Kashmir
Authors: Ullah Tariq Saiff , Firdous Syeda Sadiqa , Shier Wayne Thomas , Hussain Javeed , Shaheen Hamayun , Usman Muhammad , Akram Maryam , Khalid Abdul Nasir
Published: April 2022

Background

Wild edible mushrooms (WEM) are economically significant and used in traditional medicines worldwide. The region of Jammu and Kashmir (Western Himalayas) is enriched with the diversity of edible mushrooms, collected by the rural people for food and income generation. This is the first detailed study on diversity and ethno-medicinal uses of mushrooms from the State of Jammu and Kashmir.

Methods

Consecutive surveys were conducted to record ethnomycological diversity and socio-economic importance of wild edible mushrooms value chain in rural areas of Azad Jammu and Kashmir during 2015–2019. Ethnomycological data were collected with a semi-structured questionnaire having a set of questions on indigenous mycological knowledge and collection and retailing of wild edible mushrooms. A total of 923 informants from the study area provided the results identifying the gender, type of mushroom species, medicinal uses, and marketing of mushrooms. Diversity of mushrooms was studied by using quadrat and transect methods. Principal component analysis (PCA) and detrended correspondence analysis (DCA) were also applied to the dataset to analyse the relationship between species distribution, the underlying environmental factors, and habitat types. PCA identified the major species-specific to the sites and put them close to the sites of distribution.

Results

A total of 131 mushroom species were collected and identified during 2015–2019 from the study area. Ninety-seven species of mushrooms were reported new to the State of Azad Jammu and Kashmir. The dominant mushroom family was Russulaceae with 23 species followed by Agaricaceae, 16 species. Major mushroom species identified and grouped by the PCA were Coprinus comatus, Lactarius sanguifluus, Amanita fulva, Armillaria gallica, Lycoperdon perlatum, Lycoperdon pyriforme, and Russula creminicolor. Sparassis crispa, Pleurotus sp, and Laetiporus sulphureus were recorded most edible and medicinally significant fungi. Morels were also expensive and medicinally important among all harvested macro-fungal species. These were reported to use against common ailments and various health problems.

Conclusions

Collection and retailing of WEM contribute to improving the socio-economic status, providing alternative employment and food security to rural people of the area. These mushrooms are used as a source of food and traditional medicines among the rural informants and could be used as a potential source of antibacterial and anticancer drugs in the future.
The preemptive effects of oral pregabalin on perioperative pain management in lower limb orthopedic surgery: a systematic review and meta-analysis
Authors: Chen Zhao , Chen Jialei , Luo Rong , Jiang Jiabao , Xiang Zhou
Published: April 2022

Background

To systematically review the literature and provide a comprehensive understanding of the preemptive effects of oral pregabalin on perioperative pain management in lower limb orthopedic surgery.

Method

We searched three electronic databases for randomized controlled trials comparing the results of preoperative pregabalin and placebo in patients undergoing lower limb orthopedic surgery. Data analyses were conducted using RevMan 5.4.

Results

Twenty-one randomized controlled trials met our inclusion criteria. The cumulative opioid consumption within 24 and 48 h postoperatively in the pregabalin group was significantly less than that in the placebo group. The pooled static pain intensity at all time points within the first day was significantly lower in the pregabalin group than in the placebo group. Lower dynamic pain intensity at 48 h was detected in the pregabalin group than in the placebo group. Meanwhile, pregabalin led to a lower incidence of nausea but appeared to be associated with a higher incidence of dizziness and sedation. Subgroup analyses showed that no difference was detected between subgroups stratified by dosing regimen or pregabalin dose in the results of opioid consumption, pain intensity and incidence of complications.

Conclusion

This meta-analysis supports the use of pregabalin preoperatively in patients undergoing lower limb orthopedic surgery. However, it was wary of the resulting increase in dizziness and sedation. There is no evidence to support the continued use of pregabalin postoperatively or using more than 150 mg of pregabalin per day.

Trial registration: This study was registered on 09 November 2021 with INPLASY (registration number: INPLASY2021110031).
Gut bacteriobiota and mycobiota are both associated with Day-28 mortality among critically ill patients
Authors: Prevel Renaud , Enaud Raphaël , Orieux Arthur , Camino Adrian , Berger Patrick , Boyer Alexandre , Delhaes Laurence , Gruson Didier
Published: April 2022

Introduction

Gut microbiota is associated with host characteristics such as age, sex, immune condition or frailty and is thought to be a key player in numerous human diseases. Nevertheless, its association with outcome in critically ill patients has been poorly investigated. The aim of this study is to assess the association between gut microbiota composition and Day-28 mortality in critically ill patients.

Methods

Rectal swab at admission of every patient admitted to intensive care unit (ICU) between October and November 2019 was frozen at − 80 °C. DNA extraction was performed thanks to QIAamp® PowerFecal® Pro DNA kit (QIAgen®). V3–V4 regions of 16SRNA and ITS2 coding genes were amplified by PCR. Sequencing (2x250 bp paired-end) was performed on MiSeq sequencer (Illumina®). DADA2 pipeline on R software was used for bioinformatics analyses. Risk factors for Day-28 mortality were investigated by logistic regression.

Results

Fifty-seven patients were consecutively admitted to ICU of whom 13/57 (23%) deceased and 44/57 (77%) survived. Bacteriobiota α-diversity was lower among non-survivors than survivors (Shannon and Simpson index respectively, p < 0.001 and p = 0.001) as was mycobiota α-diversity (respectively p = 0.03 and p = 0.03). Both gut bacteriobiota and mycobiota Shannon index were independently associated with Day-28 mortality in multivariate analysis (respectively OR: 0.19, 97.5 CI [0.04–0.60], p < 0.01 and OR: 0.29, 97.5 CI [0.09–0.75], p = 0.02). Bacteriobiota β-diversity was significantly different between survivors and non-survivors (p = 0.05) but not mycobiota β-diversity (p = 0.57). Non-survivors had a higher abundance of Staphylococcus haemolyticus, Clostridiales sp., Campylobacter ureolyticus, Akkermansia sp., Malassezia sympodialis, Malassezia dermatis and Saccharomyces cerevisiae, whereas survivors had a higher abundance of Collinsella aerofaciens, Blautia sp., Streptococcus sp., Faecalibacterium prausnitzii and Bifidobacterium sp.

Conclusion

The gut bacteriobiota and mycobiota α diversities are independently associated with Day-28 mortality in critically ill patients. The causal nature of this interference and, if so, the underlying mechanisms should be further investigated to assess if gut microbiota modulation could be a future therapeutic approach.
Confirmed severe acute respiratory syndrome coronavirus 2 encephalitis in cerebrospinal fluid: a case report
Authors: Ayuningtyas Triana , Natadidjaja Ronald Irwanto , Octaviani Chyntia , Sahli Felly , Adlani Hadianti
Published: April 2022

Background

Patients with severe acute respiratory syndrome coronavirus 2 infection show various clinical manifestations, including neurological . Altered consciousness due to severe acute respiratory syndrome coronavirus 2 encephalitis is a very threatening condition if not treated immediately.

Case presentation

We present the case of a 34-year-old Asian female who tested positive for severe acute respiratory syndrome coronavirus 2 infection using a nasopharyngeal swab sample and presented with acute changes in consciousness without typical respiratory symptoms. Empiric therapy was immediately and simultaneously given with cerebrospinal fluid analysis using polymerase chain reaction, which later also showed positive results for severe acute respiratory syndrome coronavirus 2 infection.

Conclusions

It is important to consider the diagnosis of severe acute respiratory syndrome coronavirus 2 encephalitis when a patient presents with acute altered consciousness and no typical respiratory symptoms. Early empiric therapy can improve patient outcomes.
Impact of health system engagement on the health and well-being of people who use drugs: a realist review protocol
Authors: Salvalaggio Ginetta , Ferguson Lawrence , Brooks Hannah L. , Campbell Sandra , Gladue Vanessa , Hyshka Elaine , Lam Linda , Morris Heather , Nixon Lara , Springett Jane
Published: April 2022

Background

Although community-level benefits of health system engagement (i.e., health service planning, delivery, and quality improvement, engaged research and evaluation, and collaborative advocacy) are well established, individual-level impacts on the health and well-being of community members are less explored, in particular for people who use or have used illegal drugs (PWUD). Capacity building, personal growth, reduced/safer drug use, and other positive outcomes may or may not be experienced by PWUD involved in engagement activities. Indeed, PWUD may also encounter stigma and harm when interacting with healthcare and academic structures. Our objective is to uncover why, how, and under what circumstances positive and negative health outcomes occur during health system engagement by PWUD.

Methods

We propose a realist review approach due to its explanatory lens. Through preliminary exploration of literature, lived experience input, and consideration of formal theories, an explanatory model was drafted. The model describes contexts, mechanisms, and health outcomes (e.g., mental health, stable/safer drug use) involved in health system engagement. The explanatory model will be tested against the literature and iteratively refined against formal theories. A participatory lens will also be used, wherein PWUD with lived experience of health system engagement will contribute throughout all stages of the review.

Discussion

We believe this is the first realist review to explore the contextual factors and underlying mechanisms of health outcomes for PWUD who participate in health system engagement. A thorough understanding of the relevant literature and theoretical underpinnings of this process will offer insights and recommendations to improve the engagement processes of PWUD.
Incidence and outcomes of critical illness in Indigenous Peoples: a systematic review protocol
Authors: Bowker Samantha L. , Williams Kienan , Wingert Aireen , Boyd Jamie M. , Potestio Melissa L. , Gates Michelle , Wright Erica , Bagshaw Sean M.
Published: April 2022

Background

Indigenous Peoples experience health inequities across the continuum of health services. Improvements for Indigenous patients and their families during vulnerable experiences with the healthcare system may have a significant impact on the patient experience and outcomes. Improved understanding of the occurrence of critical illness in Indigenous Peoples and their use of critical care services, as a strategic priority, may aid in the development of initiatives for improving health equity. A global focus was selected to learn from Indigenous populations’ experiences with critical care, as the understanding of critical illness among Indigenous Peoples in Canada is not well understood. This protocol outlines a systematic review focused on describing the incidence of critical illness and utilization of critical care services among Indigenous Peoples.

Methods

Ovid MEDLINE/PubMed, Ovid EMBASE, Google Scholar, and Cochrane Central Register of Controlled Trials will be searched. Relevant Canadian sites for gray literature (National Collaborating Centre for Indigenous Health, First Nations Health Authority, Canadian Institutes of Health Research Institute of Indigenous Peoples’ Health, National Association of Friendship Centres, the Alberta First Nations Information Governance Centre, Métis Nation of Alberta) will also be searched. We will include studies of adults (≥18 years) either without critical illness (i.e., general population) or with critical illness (i.e., admitted to an intensive care unit (ICU)). The exposure of interest will be Indigenous identity. Primary outcome measures are ICU admission and ICU mortality. Because heterogeneity in populations, comparisons, and outcome measures is anticipated, it is likely that the findings will be summarized using a narrative synthesis. A meta-analysis will be performed if there is sufficient evidence on one or more outcomes of interest.

Discussion

This systematic review will provide a better understanding of the epidemiology, risk factors, and outcomes of critical illness and utilization of critical care services among Indigenous Peoples. The knowledge generated will be applied to a broader program of work designed to create ethical space to co-design, implement, and evaluate a culturally competent, safe, and innovative model for critical care services for Indigenous People.

Systematic review registration

PROSPERO CRD42021254661
National and sub-national trends of salt intake in Iranians from 2000 to 2016: a systematic analysis
Authors: Gholami Ali , Ghanbari Ali , Rezaei Shahabeddin , Baradaran Hamid Reza , Khatibzadeh Shahab , Parsaeian Mahboubeh , Hariri Mitra , Zamaninour Negar , Sheidaei Ali , Abdollahi Morteza , Mirmiran Parvin , Ghayour-Mobarhan Majid , Ostovar Afshin , Mohammadifard Noushin , Khosravi Alireza , Namayandeh Seyedeh Mahdieh , Farzadfar Farshad
Published: April 2022

Background

One fifth of the global burden of cardiovascular diseases (CVDs) in 2017 was attributable to excessive salt intake. As a member of the World Health Organization (WHO), Iran has committed itself to a 30% reduction in salt intake by 2025. Evidence on the amount and trend of salt intake among the Iranian population at national and sub-national levels is scarce. This study aimed to estimate the Iranian population’s salt intake during 2000–2016 at the national and sub-national levels, by sex and age groups.

Methods

Data on national and sub-national mean salt intake was obtained through systematically searching the literature and contacting the research studies’ principal investigators. Data collected through various methods were harmonized using the cross-walk method. Bayesian hierarchical and spatio-temporal-age regression models and simulation analysis were used to estimate the mean salt intake and its uncertainty interval across sex, age, year, and province.

Results

National age-sex standardized mean salt intake decreased from 10·53 g/day (95% uncertainty interval [UI]: 10·2 to 10·9) in 2000 to 9·41 (9·2 to 10·6) in 2016 (percent change: − 9·8% [− 21·1–3·1]). The age-standardized mean salt intake in women had decreased from 9·8 g/day (95% UI: 9·0–10·6) in 2000 to 9·1 g/day (8·6–9·7) in 2016 (percent change: − 6·6% [− 19·0–7·9]). The same measure in men was 11·1 g/day in 2000 (95% UI: 10·3–11·8) and 9·7 g/day (9·1–10·2) in 2016 (percent change: − 12·7% [− 23·0 – -0·9]).

Age-sex standardized mean salt intake at the sub-national level in 2016 varied from 8·0 (95% UI: 7·0–9·0) to 10·5 (10·0–11·1). The difference between the provinces with the highest and the lowest levels of salt intake in 2016 was 31·3%.

Conclusion

Salt intake decreased in Iran from 2000 to 2016, while persistently exceeding the recommended values. This declining trend was more pronounced between 2010 and 2016, which might be attributed to Iran’s compliance to WHO’s Action Plan for reducing NCDs.
Analgesic effect of iliopsoas plane block for hip fracture
Authors: Wang Chun-Guang , Yang Yang , Yang Ming-Yu , Wang Xiu-Li , Ding Yan-Ling
Published: April 2022

Background

Hip fracture and surgery are associated with moderate to severe pain, which hampers early mobilization and extends the hospital stay. Femoral nerve block and fascia iliaca compartment block could provide effective postoperative pain relief. Unfortunately, they could weaken the strength of the quadriceps muscle and increase the risk of falls. Iliopsoas plane block (IPB) is a novel motor-sparing regional technique, which targets the sensory branches of the hip joint originating from the femoral nerve. However, the analgesic effect of IPB has not been confirmed yet.

Case presentation

In the present case series, IPB and lateral femoral cutaneous nerve block were implemented under the guidance of ultrasound for eight patients with hip fractures. The median (IQR) visual analog scale (VAS) score (0–10; 0: no pain, 10: worst pain) decreased from 1.5 (0.25–2) before IPB to 0 (0–0) 0.5h after IPB at rest. The median (IQR) VAS score decreased from 8 (7–8) before IPB to 2 (1–2) 0.5h after IPB during flexion of hip 30°. Pain score was no more than one at rest and three during flexion of the hip 30° within 48h after surgery. Furthermore, the MMT grades of quadriceps strength were no less than four after IPB.

Conclusions

Our case series firstly highlights that IPB might be an effective analgesic technique for hip fracture and surgery, while retaining motor function.
Patients exposed to vancomycin-resistant enterococci during in-hospital outbreaks in a low endemic setting: a proposal for risk-based screening
Authors: Büchler Andrea C. , Ragozzino Silvio , Wicki Melanie , Spaniol Violeta , Jäger Sammy , Seth-Smith Helena M. B. , Goldenberger Daniel , Hinic Vladimira , Egli Adrian , Frei Reno , Widmer Andreas F.
Published: April 2022

Background

The optimal extent of screening of contact patients (CoPat) after exposure to patients infected or colonized with vancomycin-resistant enterococci (VRE) remains controversial.

Methods

We retrospectively developed a new risk stratification for screening patients exposed to VRE, based on data from three outbreaks—two with Enterococcus faecium vanB and one with Enterococcus faecium vanA involving 1096 CoPat—in a low endemic setting. We classified them into four risk groups: three on environmental exposure, one by healthcare exposure: high (sharing the same room/bathroom with a VRE-colonized patient), medium (hospitalization in the same room after a VRE-colonized patient’s discharge until terminal disinfection including ultraviolet C (UVc)-disinfection), low (hospitalized in the same room within three weeks before the VRE-colonized patient), and “staff” (screening of patients having the same medical care team).

Results

VRE-transmission occurred in 7.9% in the high-risk group compared to 0.6% and 0% in the medium and low risk groups. There was a significant trend to higher rates of transmission by risk level of exposure (p < 0.001). In the “staff” group, VRE transmission rate was 2.3%.

Conclusion

Based on this stratification, we recommend to focus screening of exposed CoPat on the high-risk and “staff” group, saving resources and costs, but larger studies will allow to further improve the yield of VRE screening in the outbreak setting.
The intriguing roles of Siglec family members in the tumor microenvironment
Authors: Jiang Kui-Ying , Qi Li-Li , Kang Fu-Biao , Wang Ling
Published: April 2022

Sialic acid-binding receptors are expressed on the surfaces of a variety of immune cells and have complex and diverse immunoregulatory functions in health and diseases. Recent studies have shown that Siglecs could play diverse immune and nonimmune regulatory roles in the tumor microenvironment (TME) and participate in tumor progression through various mechanisms, such as regulating tumor growth and metastasis, mediating the inflammatory response, and promoting tumor immune escape, thereby affecting the prognoses and outcomes of patients. However, depending on the cell type in which they are expressed, each Siglec member binds to corresponding ligands in the microenvironment milieu to drive diverse cell physiological and pathological processes in tumors. Therefore, we herein summarize the expression spectra and functions of the Siglec family in human diseases, particularly cancer, and highlight the possibility of therapeutic interventions targeting the TME in the future.
EGFR exon 20 insertion mutations in advanced non-small-cell lung cancer: current status and perspectives
Authors: Hou Jiabao , Li Hongle , Ma Shuxiang , He Zhen , Yang Sen , Hao Lidan , Zhou Hanqiong , Zhang Zhe , Han Jing , Wang Li , Wang Qiming
Published: April 2022

Platinum-based chemotherapy was previously the first-choice treatment for lung cancer. The discovery of epidermal growth factor receptor (EGFR) gene mutations and the development of EGFR tyrosine kinase inhibitors (TKIs) marked the beginning of the targeted therapy era for non-small-cell lung cancer (NSCLC). Thirty percent of NSCLC patients carry EGFR gene mutations. For these advanced NSCLC patients, EGFR-TKIs are currently preferred for their superior activity and survival benefits over platinum-based chemotherapy. However, therapeutic efficacy is quite different in patients with EGFR exon 20 insertion (ex20ins) mutations versus common mutations. Patients with ex20ins mutations are insensitive to EGFR-TKIs and have poor prognosis. Some drugs targeting EGFR ex20ins mutations have been approved. Here, we systematically reviewed the recent clinical research of and treatments used for EGFR ex20ins mutations, summarized the latest data on emerging therapies, and discussed future prospects and treatments.
Targeting CD47/SIRPα as a therapeutic strategy, where we are and where we are headed
Authors: Qu Tailong , Li Baiyong , Wang Yifei
Published: April 2022

Immunotherapy using PD-1 and CTLA4 inhibitors to stimulate T cell immunity has achieved significant clinical success. However, only a portion of patients benefit from T cell-based immunotherapy. Macrophages, the most abundant type of innate immune cells in the body, play an important role in eliminating tumor cells and infectious microbes. The phagocytic check point protein CD47 inhibits the phagocytic activity of macrophages through binding to SIRPα expressed on macrophages. Blockade of the interaction between CD47 and SIRPα could restore phagocytic activity and eliminate tumor cells in vitro and in vivo. In this manuscript, we review the mechanism of action and development status of agents (antibodies targeting CD47 and SIRPα, SIRPα-Fc fusion proteins, and bi-specific antibodies) that block CD47/SIRPα interaction in preclinical studies and in the clinical setting. In addition, small molecules, mRNA, and CAR-T/M that target the CD47/SIRPα axis are also reviewed in this article.
The amyloid plaque proteome in early onset Alzheimer’s disease and Down syndrome
Authors: Drummond Eleanor , Kavanagh Tomas , Pires Geoffrey , Marta-Ariza Mitchell , Kanshin Evgeny , Nayak Shruti , Faustin Arline , Berdah Valentin , Ueberheide Beatrix , Wisniewski Thomas
Published: April 2022

Amyloid plaques contain many proteins in addition to beta amyloid (Aβ). Previous studies examining plaque-associated proteins have shown these additional proteins are important; they provide insight into the factors that drive amyloid plaque development and are potential biomarkers or therapeutic targets for Alzheimer’s disease (AD). The aim of this study was to comprehensively identify proteins that are enriched in amyloid plaques using unbiased proteomics in two subtypes of early onset AD: sporadic early onset AD (EOAD) and Down Syndrome (DS) with AD. We focused our study on early onset AD as the drivers of the more aggressive pathology development in these cases is unknown and it is unclear whether amyloid-plaque enriched proteins differ between subtypes of early onset AD. Amyloid plaques and neighbouring non-plaque tissue were microdissected from human brain sections using laser capture microdissection and label-free LC–MS was used to quantify the proteins present. 48 proteins were consistently enriched in amyloid plaques in EOAD and DS. Many of these proteins were more significantly enriched in amyloid plaques than Aβ. The most enriched proteins in amyloid plaques in both EOAD and DS were: COL25A1, SMOC1, MDK, NTN1, OLFML3 and HTRA1. Endosomal/lysosomal proteins were particularly highly enriched in amyloid plaques. Fluorescent immunohistochemistry was used to validate the enrichment of four proteins in amyloid plaques (moesin, ezrin, ARL8B and SMOC1) and to compare the amount of total Aβ, Aβ40, Aβ42, phosphorylated Aβ, pyroglutamate Aβ species and oligomeric species in EOAD and DS. These studies showed that phosphorylated Aβ, pyroglutamate Aβ species and SMOC1 were significantly higher in DS plaques, while oligomers were significantly higher in EOAD. Overall, we observed that amyloid plaques in EOAD and DS largely contained the same proteins, however the amount of enrichment of some proteins was different in EOAD and DS. Our study highlights the significant enrichment of many proteins in amyloid plaques, many of which may be potential therapeutic targets and/or biomarkers for AD.
Interface astrogliosis in contact sport head impacts and military blast exposure
Authors: Babcock Katharine J. , Abdolmohammadi Bobak , Kiernan Patrick T. , Mahar Ian , Cherry Jonathan D. , Alvarez Victor E. , Goldstein Lee E. , Stein Thor D. , McKee Ann C. , Huber Bertrand R.
Published: April 2022

Exposure to military blast and repetitive head impacts (RHI) in contact sports is associated with increased risk of long-term neurobehavioral sequelae and cognitive deficits, and the neurodegenerative disease chronic traumatic encephalopathy (CTE). At present, the exact pathogenic mechanisms of RHI and CTE are unknown, and no targeted therapies are available. Astrocytes have recently emerged as key mediators of the multicellular response to head trauma. Here, we investigated interface astrogliosis in blast and impact neurotrauma, specifically in the context of RHI and early stage CTE. We compared postmortem brain tissue from former military veterans with a history of blast exposure with and without a neuropathological diagnosis of CTE, former American football players with a history of RHI with and without a neuropathological diagnosis of CTE, and control donors without a history of blast, RHI exposure or CTE diagnosis. Using quantitative immunofluorescence, we found that astrogliosis was higher at the grey-white matter interface in the dorsolateral frontal cortex, with mixed effects at the subpial surface and underlying cortex, in both blast and RHI donors with and without CTE, compared to controls. These results indicate that certain astrocytic alterations are associated with both impact and blast neurotrauma, and that different astroglial responses take place in distinct brain regions.
Harmonization of [11C]raclopride brain PET images from the HR+ and HRRT: method development and validation in human subjects
Authors: Hoye Jocelyn , Toyonaga Takuya , Zakiniaeiz Yasmin , Stanley Gelsina , Hampson Michelle , Morris Evan D.
Published: April 2022

Background

There has been an ongoing need to compare and combine the results of new PET imaging studies conducted with [11C]raclopride with older data. This typically means harmonizing data across different scanners. Previous harmonization studies have utilized either phantoms or human subjects, but the use of both phantoms and humans in one harmonization study is not common. The purpose herein was (1) to use phantom images to develop an inter-scanner harmonization technique and (2) to test the harmonization technique in human subjects.

Methods

To develop the harmonization technique (Experiment 1), the Iida brain phantom was filled with F-18 solution and scanned on the two scanners in question (HRRT, HR+, Siemens/CTI). Phantom images were used to determine the optimal isotropic Gaussian filter to harmonize HRRT and HR+ images. To evaluate the harmonization on human images (Experiment 2), inter-scanner variability was calculated using [11C]raclopride scans of 3 human subjects on both the HRRT and HR+ using percent difference (PD) in striatal non-displaceable binding potential (BPND) between HR+ and HRRT (with and without Gaussian smoothing). Finally, (Experiment 3), PDT/RT was calculated for test–retest (T/RT) variability of striatal BPND for 8 human subjects scanned twice on the HR+.

Results

Experiment 1 identified the optimal filter as a Gaussian with a 4.5 mm FWHM. Experiment 2 resulted in 13.9% PD for unfiltered HRRT and 3.71% for HRRT filtered with 4.5 mm. Experiment 3 yielded 5.24% PDT/RT for HR+.

Conclusions

The PD results show that the variability of harmonized HRRT is less than the T/RT variability of the HR+. The harmonization technique makes it possible for BPND estimates from the HRRT to be compared to (and/or combined with) those from the HR+ without adding to overall variability. Our approach is applicable to all pairs of scanners still in service.
Superior mesenteric vein reconstruction during pancreatoduodenectomy using a dilated right ovarian vein in a patient at future risk for pelvic congestion syndrome: a case report
Authors: Takahashi Yuki , Matsuo Kenichi , Oyama Hideyuki , Sekine Ryuichi , Nakamura Akihiro , Uchida Tsuneyuki , Makuuchi Mikio , Tanaka Kuniya
Published: April 2022

Background

Pancreatoduodenectomy including resection of the superior mesenteric vein (SMV) is increasingly performed for right-sided pancreatic ductal adenocarcinoma invading the wall of that vessel. Various venous grafts may be chosen for reconstruction. We present a woman with pancreatic cancer who underwent such a pancreatoduodenectomy with venous reconstruction using a dilated right ovarian vein.

Case presentation

A 71-year-old woman with cancer involving the pancreatic head, uncinate process, and SMV underwent pancreatoduodenectomy with SMV resection. Reconstruction used a portion of the right ovarian vein that was markedly dilated and had placed her at risk for pelvic congestion syndrome (PCS). Graft patency was confirmed 8 months after surgery. She now finished receiving adjuvant chemotherapy and has no symptoms of PCS.

Conclusion

If an ovarian vein has sufficient diameter, it can be used to reconstruct the resected segment of the SMV during pancreatoduodenectomy in suitable patients.
A Framework for Clinicians to Improve the Decision-Making Process in Return to Sport
Authors: Yung Kate K. , Ardern Clare L. , Serpiello Fabio R. , Robertson Sam
Published: April 2022

Return-to-sport (RTS) decisions are critical to clinical sports medicine and are often characterised by uncertainties, such as re-injury risk, time pressure induced by competition schedule and social stress from coaches, families and supporters. RTS decisions have implications not only for the health and performance of an athlete, but also the sports organisation. RTS decision-making is a complex process, which relies on evaluating multiple biopsychosocial factors, and is influenced by contextual factors. In this narrative review, we outline how RTS decision-making of clinicians could be evaluated from a decision analysis perspective. To begin with, the RTS decision could be explained as a sequence of steps, with a decision basis as the core component. We first elucidate the methodological considerations in gathering information from RTS tests. Second, we identify how decision-making frameworks have evolved and adapt decision-making theories to the RTS context. Third, we discuss the preferences and perspectives of the athlete, performance coach and manager. We conclude by proposing a framework for clinicians to improve the quality of RTS decisions and make recommendations for daily practice and research.
The protective effect of β-cryptoxanthin against cyclophosphamide-induced lung injury in adult male albino rats
Authors: Badawi Marwa Sayed
Published: April 2022

Background

Cyclophosphamide (CYP) is an anticancer agent widely used in chemotherapy. It has been suggested that CYP causes toxicity in many organs, including the lungs and testes. Many studies have indicated that some antioxidants have possible protective effects against CYP’s side effects. β-cryptoxanthin (BCX), a major carotenoid of potential interest for health, is known for its antioxidant activities. This study aimed to investigate the protective effect of BCX on CYP-induced lung injury in rats using histologic and biochemical methods.

Methods

Forty adult male albino rats were divided into 4 groups: Group I served as the control group. Group II received BCX orally in a dose of 4 mg/kg per day for 7 days. Group III received a single dose (200 mg/kg) of CYP intraperitoneally (i.p.) on the 7th day of the study. Group IV received (CYP + BCX). On the 8th day of the experiment, lung tissues were collected for histopathological examinations. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were also determined in all dissected tissues.

Results

Pretreatment with BCX ameliorated lung morphological changes noticed in CYP group and the levels of MDA and MPO were significantly decreased whereas those of GSH, GSH-Px and SOD were significantly increased.

Conclusions

BCX provides a protective effect against CYP-induced lung injury by reducing oxidative stress and pulmonary fibrosis.
In silico studies on the interaction of four cytotoxic compounds with angiogenesis target protein HIF-1α and human androgen receptor and their ADMET properties
Authors: Ngbolua Jean-Paul Koto-Te-Nyiwa , Kilembe Jason T. , Matondo Aristote , Ashande Colette Masengo , Mukiza Janvier , Nzanzu Célestin Mudogo , Ruphin Fatiany Pierre , Baholy Robijaona , Mpiana Pius T. , Mudogo Virima
Published: April 2022

Background

Cancer is a significant public health problem worldwide and constitutes the second leading cause of death after cardiovascular disease. This study was thus designed to identify new natural compounds from Malagasy medicinal plants traditionally used to treat cancer.

Methods

In silico analyses by molecular docking to model ligand–protein interactions, and by SwissADME and ADMET webservers to establish the pharmacokinetic profile of the four investigated compounds in interaction with the angiogenesis target protein HIF-1α/breast cancer (PDB ID: 3KCX) and human androgen receptor/prostate cancer (PDB ID: 1E3G) were performed.

Results

The docking results show that the HIF-1α receptor has the best binding energy when it interacts with compound 1 (1′,4-dihydroxy-2,3′-dimethyl-1,2′-binapthyl-5,5′,8,8′-tetraone: − 8.49 kcal/mol) followed by compound 3 [(E)-5,6-dimethyl-2-(2-methyl-3-(prop-1-enyl)phenyl)-2H-chromene: -8.43 kcal/mol], compound 2 (6′-ethoxy-1′3′-dihydroxy-4,6-dimethyl-1,2′-binaphthyl-2,5′,8,8′-tetraone: − 7.80 kcal/mol) and compound 4 (methyl 10-hydroxy-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxylate: − 7.63 kcal/mol). The receptor 1E3G displayed poor binding affinity energy to all tested compounds with energy value above − 11.99 kcal/mol (co-crystal). Based on the H-bonding interaction, ligands 1 and 2 displayed a good pharmacophore profiles to both protein targets 3KCX and 1E3G. Ligand 3 does not interact with the selected receptors via hydrogen bonds. The pharmacokinetic profile of these phyto-compounds revealed that they are orally active and safe. They were isolated and their chemical structures were elucidated previously by our team using chromatographic and spectroscopic techniques (LC/MS/NMR).

Conclusions

The ligands 1 and 2 can be considered as hits since in addition to their thermodynamic stability with the receptors; they presented a good pharmacokinetic profile and could thus be useful as an alternative therapy in breast and prostate cancer. This study offers a strong potential in developing new, cost-effective, and safe plant-based natural drugs against cancer.