bluuebunny/crossref_metadata_2025 huggingface dataset:
Comorbidities and psychosocial factors as correlates of self-reported falls in a nationwide sample of community-dwelling people aging with HIV in Germany
Authors: Drewes Jochen , Ebert Jennifer , Langer Phil C. , Kleiber Dieter , Gusy Burkhard
Published: August 2021

Background

Falls are a frequent health problem with potentially severe consequences among the elderly. Due to the aging HIV population, there is a growing interest in falls as a geriatric syndrome in HIV research and clinical practice. Previous studies found rather high prevalences of falls in this population and focused on biomedical and demographic risk factors for falls. Psychosocial risk factors like stigma, social support or loneliness were not previously assessed as correlates of fall events in this population.

Methods

We assessed self-reported fall frequency in the past 12 months in a nationwide sample of 897 community-dwelling people aged 50 years or older living with HIV in Germany using a cross-sectional study design. We calculated odds of any fall for sociodemographic and HIV-related variables in bivariate analyses and for comorbidities, and psychosocial variables in bivariate and adjusted analyses.

Results

Eighteen percent of our participants reported at least one fall in the preceding 12 months, 12 % reported recurring falls. A lower socioeconomic status, being single and living alone were significantly associated with a higher risk for falling. An AIDS diagnosis was related to fall risk, but time since diagnosis and a detectable viral load were not. Reporting at least one comorbidity increased fall risk in our sample 2.5 times (95% CI: 1.59; 3.97). The strongest association with fall risk was found for diseases of the central nervous system, heart disease, rheumatism, osteoporosis, and chronic pain. Experienced HIV stigma (AOR: 2.11; 95% CI: 1.58; 2.83) and internalized HIV stigma (AOR: 1.43; 95% CI: 1.12; 1.85), as well as social support (AOR: .92; 95% CI: .86; .99) and loneliness (AOR: 1.51; 95% CI: 1.22; 1.87) were significantly related to fall risk in bivariate and adjusted analyses.

Conclusions

We found a low prevalence of falls in our sample of community-dwelling people aging with HIV. Our results show evidence for a strong association between comorbidity and falling, and between psychosocial factors and falling. Especially the strong association between experienced HIV stigma and fall risk is noteworthy and adds falls to the list of health outcomes affected by HIV stigma.
Influenza vaccination should have no border: cost-effectiveness of cross-border subsidy
Authors: Yamin Dan , Kahana Dor , Shahmoon Edan , Fitzpatrick Meagan C. , Galvani Alison P.
Published: August 2021

Background

Influenza is a substantial cause of morbidity and mortality for Israel and the Palestinian territory. Given the extensive interaction between the two populations, vaccination in one population may indirectly benefit the other via reduced transmission. Due to the mobility and extensive contacts, Palestinians employed in Israel could be a prime target for vaccination.

Methods

To evaluate the epidemiological and the economic benefits conferred by vaccinating Palestinians employed in Israel, we developed a model of influenza transmission within and between Israel and the West Bank. We parameterized the contact patterns underlying transmission by conducting a survey among Palestinians employed in Israel, and integrating survey results with traffic patterns and socio-demographic data.

Results

Vaccinating 50% of Palestinian workers is predicted to reduce the annual influenza burden by 28,745 cases (95% CI: 15,031-50,717) and 37.7 deaths (95% CI: 19·9–65·5) for the Israeli population, and by 32,9900 cases (95% CI: 14,379-51,531) and 20.2 deaths (CI 95%: 9·8–31·5) for the Palestinian population. Further, we found that as the indirect protection was so substantial, funding such a vaccination campaign would be cost-saving from the Israeli Ministry of Health perspective.

Conclusions

Offering influenza vaccination to Palestinians employed in Israel could efficiently reduce morbidity and mortality within both Israel and the Palestinian territory.
Abnormalities of foot and ankle alignment in individuals with chronic ankle instability: a systematic review
Authors: Kobayashi Takumi , Koshino Yuta , Miki Takahiro
Published: August 2021

Background

To prevent recurrent ankle sprain, it is important to clarify the pathology of chronic ankle instability (CAI). An association has been reported between CAI and abnormalities of foot posture and ankle alignment. There is no consensus on the types of these abnormalities that occur in individuals with CAI. The objective of this systematic review is to clarify the relevance of abnormality of foot posture and ankle alignment for CAI.

Methods

A systematic computerized literature search was performed of the PubMed, CINAHL, SPORTDiscus, Web of Science, and the Cochrane Register of Clinical Trials databases. The selected studies either compared CAI patients with a control group or CAI ankles with contralateral healthy ankles and specifically reported foot posture and alignment of the ankle in the outcomes. They were written in English and published prior to June 2021. The methodological quality of the included studies was evaluated using a 16-question index. Data were extracted independently by two reviewers, and the certainty of evidence was assessed using GRADE approach.

Results

Sixteen studies including 872 patients of high to low methodological quality were included. These showed there was significant anterior displacement and internal rotation of the talus in CAI ankles (low evidence), but there was no consensus on fibular alignment or foot posture.

Conclusions

This review showed there was significant anterior displacement and internal rotation of the talus in CAI ankles but found no consensus on the characteristics of fibular and foot alignment. Further investigations are required to clarify the characteristic foot and ankle malalignment in CAI to facilitate the development of efficient interventions.
Evaluation of factors affecting external tibial torsion in patients with cerebral palsy
Authors: Min Jae Jung , Kwon Soon-Sun , Kim Kyu Tae , Choi Young , Sung Ki Hyuk , Lee Kyoung Min , Park Moon Seok
Published: August 2021

Background

Gait deviation and associated torsional problems are common in patients with cerebral palsy (CP). Although femoral anteversion in CP has been extensively reviewed in previous studies, only a few studies have focused on tibial torsion. Therefore, this study aimed to evaluate tibial torsion in patients with CP and investigate the affecting factors.

Methods

Consecutive patients with cerebral palsy who underwent 3-dimensional computed tomography for the assessment of rotational profiles were reviewed. Femoral anteversion and tibial torsion were measured, and the demographic characteristics of the patients were recorded. A linear mixed model was implemented to overcome the retrospective nature of the study.

Results

After the implementation of inclusion and exclusion criteria, 472 patients were enrolled for this study. With age, external tibial torsion increased, while femoral anteversion decreased. The factors affecting external tibial torsion were increased femoral anteversion (p = 0.0057), increased age (p < 0.0001), higher Gross Motor Function Classification System (GMFCS) level (p < 0.0001), and involved/uninvolved limbs of hemiplegia (p = 0.0471/p = 0.0047).

Conclusions

Older age, GMFCS level IV/V, hemiplegia, and increased femoral anteversion were the independent risk factors of increasedexternaltibial torsion; therefore, performing an imaging study is recommended for assessing the extent of tibial torsion in patients with such characteristics.
Exploring the relationship between pain intensity and knee moments in participants with medial knee osteoarthritis: a cross-sectional study
Authors: Huang Chen. , Chan Ping-Keung. , Chiu Kwong-Yuen. , Yan Chun-Hoi. , Yeung Shun-Shing. , Fu Siu N.
Published: August 2021

Background

High biomechanical loading is believed to be a risk factor to pain in people with knee osteoarthritis (OA), but controversial findings have been reported on the relationship between external knee adduction moment (KAM) and pain. A more comprehensive analysis considering other factor such as external knee flexion moment (KFM) could help better reveal this relationship. This study explored the relationship between external knee adduction moment and pain intensity in participants with knee osteoarthritis (OA) using an integrated path analysis model.

Methods

This was a cross-sectional study based on laboratory setting. Forty-seven participants with clinical and radiographic medial knee OA were analyzed for their external knee adduction moment (KAM) and knee flexion moment (KFM) during walking using a motion analysis system. Pain intensity was measured by visual analogue scale (VAS) and the pain subscale of the Knee Injury and Osteoarthritis Outcome Score. Varus/valgus alignment was captured and quantified using a bi-planar X-ray system. Using a path analysis model, the relationships between pain intensity, KAM, KFM, OA radiographic severity, knee varus angle and walking speed were examined.

Results

The proposed path model met the goodness-of-fit criteria. Based on this model, KAM had a negative effect on VAS pain indirectly through the mediation of KFM. The model indicated KAM and KFM were negatively related to one another; and KFM was positively related to VAS. The KAM index, defined as (KAM/ (KAM + KFM)), was negatively related to VAS.

Conclusions

Path analysis enabled the construction of a more integrated pathokinematic framework for people with knee OA. The KAM index which reflected the load sharing on the frontal and sagittal planes also revealed its relationship with pain. Re-distribution of mechanical loading from frontal to sagittal plane might be a strategy for pain avoidance associated with mechanical irritation.
Proactive integrated virtual healthcare resource use in primary care
Authors: Haun Jolie N. , Cotner Bridget A. , Melillo Christine , Panaite Vanessa , Messina William , Patel-Teague Shilpa , Zilka Brian
Published: August 2021

Background

Proactive integrated virtual healthcare resource (VHR) use can improve efficiency, maximize resource capacity for delivering optimal coordinated care and improve patient outcomes. Proactive integrated VHR use is vital for delivering high quality care. Our objectives were to identify proactive integrated VHR use among primary care teams, best practices and targeted implementation strategies to promote proactive integrated VHR use.

Methods

This is a mixed-method descriptive study. We employed a community-based participatory approach to collect data and the Consolidated Framework for Implementation Research to analyze and contextualize findings. A cross-sectional sample of primary care team members (n = 65) from a Department of Veterans Affairs medical center participated in focus groups, follow-up interviews (n = 16), and respond to self-report surveys. Operational subject matter experts (n = 15) participated in informant interviews.

Results

Survey data described current use and factors that influenced singular VHR use and were convergent with qualitative findings. Focus group and interview data described no evidence of proactive integrated VHR use. Differences and similarities were identified between both utilization groups, such as facilitators and barriers, recommendations, patient education and preferred implementation strategies. All groups reported issues around VHR availability knowledge and access and functionality. Participants identified the need for best practices that are specific to care tasks and performance measures. Expert informant interviews identified a list of VHR tools that could be proactively integrated across the healthcare continuum.

Conclusions

Health systems are leveraging technologies to proactively integrate VHR to maximize information exchange, clinical decision support and patient engagement. VHR is critical during global pandemics, such as COVID-19, to maintain access to care coordination and delivery while abiding by public health recommendations. Though recent requirements for reducing contact create an intrinsic motivation, cultural change through education and best practices of proactive integrated use across the healthcare continuum is needed to create a culture of VHR super users.
Quality improvement studies in nursing homes: a scoping review
Authors: Toles Mark , Colón-Emeric Cathleen , Moreton Elizabeth , Frey Lauren , Leeman Jennifer
Published: August 2021

Background

Quality improvement (QI) is used in nursing homes (NH) to implement and sustain improvements in patient outcomes. Little is known about how QI strategies are used in NHs. This lack of information is a barrier to replicating successful strategies. Guided by the Framework for Implementation Research, the purpose of this study was to map-out the use, evaluation, and reporting of QI strategies in NHs.

Methods

This scoping review was completed to identify reports published between July 2003 through February 2019. Two reviewers screened articles and included those with (1) the term “quality improvement” to describe their methods, or reported use of a QI model (e.g., Six Sigma) or strategy (e.g., process mapping) (2), findings related to impact on service and/or resident outcomes, and (3) two or more NHs included. Reviewers extracted data on study design, setting, population, problem, solution to address problem, QI strategies, and outcomes (implementation, service, and resident). Vote counting and narrative synthesis were used to describe the use of QI strategies, implementation outcomes, and service and/or resident outcomes.

Results

Of 2302 articles identified, the full text of 77 articles reporting on 59 studies were included. Studies focused on 23 clinical problems, most commonly pressure ulcers, falls, and pain. Studies used an average of 6 to 7 QI strategies. The rate that strategies were used varied substantially, e.g., the rate of in-person training (55%) was more than twice the rate of plan-do-study-act cycles (20%). On average, studies assessed two implementation outcomes; the rate these outcomes were used varied widely, with 37% reporting on staff perceptions (e.g., feasibility) of solutions or QI strategies vs. 8% reporting on fidelity and sustainment. Most studies (n = 49) reported service outcomes and over half (n = 34) reported resident outcomes. In studies with statistical tests of improvement, service outcomes improved more often than resident outcomes.

Conclusions

This study maps-out the scope of published, peer-reviewed studies of QI in NHs. The findings suggest preliminary guidance for future studies designed to promote the replication and synthesis of promising solutions. The findings also suggest strategies to refine procedures for more effective improvement work in NHs.
Cost analysis of eye bank versus surgeon prepared endothelial grafts
Authors: Pagano Luca , Gadhvi Kunal A , Parekh Mohit , Coco Giulia , Levis Hannah J , Ponzin Diego , Ferrari Stefano , Virgili Gianni , Kaye Stephen B , Edwards Rhiannon T , Romano Vito
Published: August 2021

Background

Selective lamellar corneal transplantation (keratoplasty) has overtaken full thickness penetrating keratoplasty as the graft choice for endothelial failure. Even more recently eye bank prepared tissues are becoming increasing popular as a way to reduce the risks of tissue loss and stress during endothelial keratoplasty preparation in the surgical theatre. This study compares costs between surgeon and eye bank prepared tissues for Descemet’s stripping automated endothelial keratoplasty (DSAEK) and Descemet’s membrane endothelial keratoplasty (DMEK).

Methods

Retrospective study conducted at the Royal Liverpool University Hospital including endothelial keratoplasties with a minimum of 6 months follow-up time. Cost analysis included surgical expenses, tissue acquisition fees, cost of patient’s ward admission and out-patient expenses, including cost of re-bubbling procedures, costs of visits, anterior segment imaging and optometrist visits within the first 6 months follow-up.

Results

Ninety-eight eyes of 98 patients were included in the study of which 42 underwent DSAEK surgery and 56 DMEK surgery. Cost analysis of surgical expenses in the DSAEK group showed a significant difference between using surgeon prepared and eye bank prepared tissue (£3866 ± 296 and £4389 ± 360, respectively;p < 0.01) and the same was found in the DMEK group (£3682 ± 167 and £4162 ± 167 for surgeon prepared and eye bank prepared tissues, respectively;p < 0.01). Cost of out-patient visits did not differ significantly in either group.

Conclusions

At the Royal Liverpool University Hospital, eye bank prepared tissues had higher surgical expenses compared to those prepared by the surgeon, while the post-operative care expenses were similar between the two groups.
Genome-wide association study followed by trans-ancestry meta-analysis identify 17 new risk loci for schizophrenia
Authors: Liu Jiewei , Li Shiwu , Li Xiaoyan , Li Wenqiang , Yang Yongfeng , Guo Suqin , Lv Luxian , Xiao Xiao , Yao Yong-Gang , Guan Fanglin , Li Ming , Luo Xiong-Jian
Published: August 2021

Background

Over 200 schizophrenia risk loci have been identified by genome-wide association studies (GWASs). However, the majority of risk loci were identified in populations of European ancestry (EUR), potentially missing important biological insights. It is important to perform 5 GWASs in non-European populations.

Methods

To identify novel schizophrenia risk loci, we conducted a GWAS in Han Chinese population (3493 cases and 4709 controls). We then performed a large-scale meta-analysis (a total of 143,438 subjects) through combining our results with previous GWASs conducted in EAS and EUR. In addition, we also carried out comprehensive post-GWAS analysis, including heritability partitioning, enrichment of schizophrenia associations in tissues and cell types, trancscriptome-wide association study (TWAS), expression quantitative trait loci (eQTL) and differential expression analysis.

Results

We identified two new schizophrenia risk loci, including associations in SHISA9 (rs7192086, P = 4.92 × 10-08) and PES1 (rs57016637, P = 2.33 × 10−11) in Han Chinese population. A fixed-effect meta-analysis (a total of 143,438 subjects) with summary statistics from EAS and EUR identifies 15 novel genome-wide significant risk loci. Heritability partitioning with linkage disequilibrium score regression (LDSC) reveals a significant enrichment of schizophrenia heritability in conserved genomic regions, promoters, and enhancers. Tissue and cell-type enrichment analyses show that schizophrenia associations are significantly enriched in human brain tissues and several types of neurons, including cerebellum neurons, telencephalon inhibitory, and excitatory neurons. Polygenic risk score profiling reveals that GWAS summary statistics from trans-ancestry meta-analysis (EAS + EUR) improves prediction performance in predicting the case/control status of our sample. Finally, transcriptome-wide association study (TWAS) identifies risk genes whose cis-regulated expression change may have a role in schizophrenia.

Conclusions

Our study identifies 17 novel schizophrenia risk loci and highlights the importance and necessity of conducting genetic study in different populations. These findings not only provide new insights into genetic etiology of schizophrenia, but also facilitate to delineate the pathophysiology of schizophrenia and develop new therapeutic targets.
Isolation and identification of exosomes from feline plasma, urine and adipose-derived mesenchymal stem cells
Authors: Li Dongsheng , Luo Huina , Ruan Huimin , Chen Zhisheng , Chen Shengfeng , Wang Bingyun , Xie Yong
Published: August 2021

Background

Exosomes, internal proteins, lipids, and nucleic acids coated by phospholipid bilayer membranes, are one type of small extracellular vesicles, which can mediate cell-cell communication. In recent years, exosomes have gained considerable scientific interest due to their widely applied prospect in the diagnosis and therapeutics of human and animal diseases. In this study, we describe for the first time a feasible method designed to isolate and characterize exosomes from feline plasma, urine and adipose-derived mesenchymal stem cells.

Results

Exosomes from feline plasma, urine and adipose-derived mesenchymal stem cells were successfully isolated by differential centrifugation. Quantification and sizing of exosomes were assessed by transmission electron microscopy, flow nano analysis and western blotting. Detected particles showed the normal size (30–100 nm) and morphology described for exosomes, as well as presence of the transmembrane protein (TSG101, CD9, CD63, and CD81) known as exosomal marker.

Conclusions

The results suggest that differential centrifugation is a feasible method for isolation of exosomes from different types of feline samples. Moreover, these exosomes can be used to further diagnosis and therapeutics in veterinary pre-clinical and clinical studies.
Efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria among children in Africa: a systematic review and meta-analysis of randomized control trials
Authors: Assefa Dawit Getachew , Yismaw Gizachew , Makonnen Eyasu
Published: August 2021

Background

Emergence ofPlasmodium falciparumresistance to artemisinin and its derivatives poses a threat to the global effort to control malaria. The emergence of anti-malarial resistance has become a great public health challenge and continues to be a leading threat to ongoing malaria control efforts. The aim of this review was to synthesize available evidence on the efficacy of dihydroartemisinin-piperaquine (DHA-PQ) compared to artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria among children in Africa.

Methods

A systematic literature search was done to identify relevant articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Central Register of Controlled Trials’ database (CENTRAL) for retrieving randomized control trials comparing efficacy of DHA-PQ and AL for treatment of uncomplicated falciparum malaria in African children. The search was performed from August 2020 to April 2021. Using Rev-Man software (V5.4.1), R-studio and Comprehensive Meta-analysis software version 3, the extracted data from eligible studies were pooled as risk ratio (RR) with 95% confidence interval (CI).

Results

In this review, 25 studies which involved a total of 13,198 participants were included. PCR-unadjusted treatment failure in children aged between 6 months and 15 years was significantly lower in the DHA-PQ treatment arm on day 28 than that of AL (RR 0.14, 95% CI 0.08–0.26; participants = 1302; studies = 4; I2 = 0%, high quality of evidence). Consistently, the PCR-adjusted treatment failure was significantly lower with DHA-PQ treatment group on day 28 (RR 0.45, 95% CI 0.29–0.68; participants = 8508; studies = 16; I2 = 51%, high quality of evidence) and on day 42 (RR 0.60, 95% CI 0.47–0.78; participants = 5959; studies = 17; I2 = 0%, high quality of evidence). However, the efficacy was ≥ 95% in both treatment groups on day 28.

Conclusion

From this review, it can be concluded that DHA-PQ reduces new infection and recrudescence on days 28 and 42 more than AL. This may trigger DHA-PQ to become a first-line treatment option.
Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal
Authors: Wang Zhenqing , Chen Liang , Ma Yiqun , Li Xilei , Hu Annan , Wang Huiren , Wang Wenxing , Li Xiaomin , Tian Bo , Dong Jian
Published: August 2021

The clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8+ cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy.
Development of an anti-infective coating on the surface of intraosseous implants responsive to enzymes and bacteria
Authors: Liao Xin , Yu Xingfang , Yu Haiping , Huang Jiaqi , Zhang Bi , Xiao Jie
Published: August 2021

Background

Bacterial proliferation on the endosseous implants surface presents a new threat to the using of the bone implants. Unfortunately, there is no effective constructed antibacterial coating which is bacterial anti-adhesion substrate-independent or have long-term biofilm inhibition functions.

Methods

Drug release effect was tested in Chymotrypsin (CMS) solution andS. aureus. We used bacterial inhibition rate assays and protein leakage experiment to analyze the in vitro antibacterial effect of (Montmorillonite/Poly-l-lysine-Chlorhexidine)10[(MMT/PLL-CHX)10] multilayer film. We used the CCK-8 assay to analyze the effect of (MMT/PLL-CHX)10multilayer films on the growth and proliferation of rat osteoblasts. Rat orthopaedic implant-related infections model was constructed to test the antimicrobial activity effect of (MMT/PLL-CHX)10multilayer films in vivo.

Results

In this study, the (MMT/PLL-CHX)10multilayer films structure were progressively degraded and showed well concentration-dependent degradation characteristics following incubation withStaphylococcus aureusand CMS solution. Bacterial inhibition rate assays and protein leakage experiment showed high levels of bactericidal activity. While the CCK-8 analysis proved that the (MMT/PLL-CHX)10multilayer films possess perfect biocompatibility. It is somewhat encouraging that in the in vivo antibacterial tests, the K-wires coated with (MMT/PLL-CHX)10multilayer films showed lower infections incidence and inflammation than the unmodified group, and all parameters are close to SHAM group.

Conclusion

(MMT/PLL-CHX)10multilayer films provides a potential therapeutic method for orthopaedic implant-related infections.
Artificial exosomes for translational nanomedicine
Authors: Li Yong-Jiang , Wu Jun-Yong , Liu Jihua , Xu Wenjie , Qiu Xiaohan , Huang Si , Hu Xiong-Bin , Xiang Da-Xiong
Published: August 2021

Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes. Major types of artificial exosomes include ‘nanovesicles (NVs)’, ‘exosome-mimetic (EM)’ and ‘hybrid exosomes (HEs)’, which are obtained by top-down, bottom-up and biohybrid strategies, respectively. Artificial exosomes are powerful alternatives to natural exosomes for drug delivery. Here, we outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations and future perspectives. The development of artificial exosomes holds great values for translational nanomedicine.
Closing gaps in histoplasmosis: clinical characteristics and factors associated with probable/histoplasmosis in HIV/AIDS hospitalized patients, a retrospective cross-sectional study in two tertiary centers in Pereira, Colombia
Authors: Hoyos Pulgarin Julián Andrés , Alzate Piedrahita John Alexander , Moreno Gómez German Alberto , Sierra Palacio Juan Felipe , Ordoñez Karen Melissa , Arias Ramos Deving
Published: August 2021

Background

The HIV pandemic continues to cause a high burden of morbidity and mortality due to delayed diagnosis. Histoplasmosis is prevalent in Latin America and Colombia, is difficult to diagnose and has a high mortality. Here we determined the clinical characteristics and risk factors of histoplasmosis in people living with HIV (PLWH) in Pereira, Colombia.

Materials and methods

This was a retrospective cross-sectional study (2014–2019) involving two tertiary medical centers in Pereira, Colombia. People hospitalized with HIV were included. Histoplasma antigen detection was performed in urine samples. Probable histoplasmosis was defined according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group/National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria.

Results

172 HIV-infected patients were analyzed. Histoplasmosis was confirmed in 29% (n = 50/172) of patients. The logistic regression analysis showed that the risk factors for histoplasmosis were pancytopenia (OR 4.1, 95% CI 1.6–10.3, P = 0.002), < 50 CD4 + cells/μL (OR 3.1, 95% CI 1.3–7.3, P = 0.006) and Aspartate transaminase (AST) levels > 46 IU/L (OR 3.2, 95% CI 1.3–8, P = 0.010).

Conclusions

Histoplasmosis is highly prevalent in hospitalized patients with HIV in Pereira, Colombia. The clinical findings are nonspecific, but there are some clinical abnormalities that can lead to suspicion of the disease, early diagnosis and prompt treatment. Urine antigen detection is useful for diagnosis, but is not widely available. An algorithmic approach is proposed for low-resource clinical settings.
DNA aptamer against EV-A71 VP1 protein: selection and application
Authors: Zou Xinran , Wu Jing , Gu Jiaqi , Shen Li , Mao Lingxiang
Published: August 2021

Background

Enterovirus 71 (EV-A71) is a highly infectious pathogen associated with hand, foot and mouth disease, herpangina, and various neurological complications, so it is important for the early detection and treatment of EV-A71. An aptamer is a nucleotide sequence that screened in vitro by the technology named systematic evolution of ligands by exponential enrichment technology (SELEX). Similar to antibodies, aptamers can bind to the targets with high specificity and affinity. Besides, emerging aptamers have many advantages comparing with antibodies, such as ease of synthesis and modification, having a wide variety of target materials, low manufacturing cost and easy flexibility in amending. Therefore, aptamers are promising in virus detection and anti-virus therapy.

Methods

Aptamers were selected by SELEX. Specificity, affinity and second structure were used to characterize the selected aptamers. Chemiluminescence was adopted to build an aptamer-based detection method for EV-A71. Cytopathogenic effects trial, the level of intracellular EV-A71 RNA and protein expression were used to evaluate the antiviral effect of the selected aptamers.

Results

Three DNA aptamers with high specificity and affinity for EV-A71structual protein VP1 were screened out. A rapid chemiluminutesescence aptamer biosensor for EV-A71 detection was designed out. The selected aptamers could inhibit the RNA replication and protein expression of EV-A71 in RD cells and ameliorate the cytopathogenic effects.

Conclusions

The aptamers against EV-A71 have the potentiality to be applied as attractive candidates used for EV-A71 detection and treatment in the future.
Silica-coated magnetic nanoparticles activate microglia and induce neurotoxic d-serine secretion
Authors: Shin Tae Hwan , Lee Da Yeon , Manavalan Balachandran , Basith Shaherin , Na Yun-Cheol , Yoon Cheolho , Lee Hyeon-Seong , Paik Man Jeong , Lee Gwang
Published: August 2021

Background

Nanoparticles have been studied for brain imaging, diagnosis, and drug delivery owing to their versatile properties due to their small sizes. However, there are growing concerns that nanoparticles may exert toxic effects in the brain. In this study, we assessed direct nanotoxicity on microglia, the resident macrophages of the central nervous system, and indirect toxicity on neuronal cells exerted by silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)].

Methods

We investigated MNPs@SiO2(RITC)-induced biological changes in BV2 murine microglial cellsviaRNA-sequencing-based transcriptome analysis and gas chromatography-mass spectrometry-based intracellular and extracellular amino acid profiling. Morphological changes were analyzed by transmission electron microscopy. Indirect effects of MNPs@SiO2(RITC) on neuronal cells were assessed by Transwell-based coculture with MNPs@SiO2(RITC)-treated microglia. MNPs@SiO2(RITC)-induced biological changes in the mouse brainin vivowere examined by immunohistochemical analysis.

Results

BV2 murine microglial cells were morphologically activated and the expression of Iba1, an activation marker protein, was increased after MNPs@SiO2(RITC) treatment. Transmission electron microscopy analysis revealed lysosomal accumulation of MNPs@SiO2(RITC) and the formation of vesicle-like structures in MNPs@SiO2(RITC)-treated BV2 cells. The expression of several genes related to metabolism and inflammation were altered in 100 µg/ml MNPs@SiO2(RITC)-treated microglia when compared with that in non-treated (control) and 10 µg/ml MNPs@SiO2(RITC)-treated microglia. Combined transcriptome and amino acid profiling analyses revealed that the transport of serine family amino acids, including glycine, cysteine, and serine, was enhanced. However, only serine was increased in the growth medium of activated microglia; especially, excitotoxicD-serine secretion from primary rat microglia was the most strongly enhanced. Activated primary microglia reduced intracellular ATP levels and proteasome activity in cocultured neuronal cells, especially in primary cortical neurons,via D-serine secretion. Moreover, ubiquitinated proteins accumulated and inclusion bodies were increased in primary dopaminergic and cortical neurons cocultured with activated primary microglia.In vivo, MNPs@SiO2(RITC),D-serine, and ubiquitin aggresomes were distributed in the MNPs@SiO2(RITC)-treated mouse brain.

Conclusions

MNPs@SiO2(RITC)-induced activation of microglia triggers excitotoxicity in neuronsvia D-serine secretion, highlighting the importance of neurotoxicity mechanisms incurred by nanoparticle-induced microglial activation.
Application of impedance measurement to investigate in vitro inhalation toxicity of bacteria
Authors: Klar Stefanie , Poether Dierk-Christoph , Reinert Jessica , Hüttig Nicole , Linsel Gunter , Jäckel Udo
Published: August 2021

Background

Workers of agriculture and intensive life stock farming are exposed to highly contaminated workplaces. Bioaerosol exposures are suspected to trigger respiratory health effects of the workers. So far, risk evaluation of bioaerosols has been assessed through the infectivity of comprising biological agents that is classified in Europe by four risk groups according to the criteria of Directive 2000/54EC of the European Parliament. However, this directive additionally requires the risk assessment of allergenic and toxigenic effects without further elaboration. The aim of our study was to establish an in vitro screening system that is able to measure inhalative toxic effects of bacteria and their metabolites.

Methods

In this study, we analyzed three bacterial toxins and five culture supernatants of selected bacteria with known toxicity as model agents exposed to the lung epithelial cell line NuLi-1. We used electrical cell-substrate impedance sensing (ECIS) method to monitor real-time cell changes and the viability test Prestoblue™.

Results

We confirmed concentration dependent cytotoxic effects of the selected toxins in NuLi-1 cells over a period of up to 48 h. Each toxin resulted in a different but specific impedance profile over time according to their mode of action, whereas viability assay showed the metabolic activity of the cells at a chosen time point without revealing any information on their mode of action. Furthermore, dose-response-relationships were monitored. Tested model bacteria (Streptoccous pneumoniae, Acinetobacter radioresistens, Aerococcus viridans, Aeromonas hydrophila) reacted according to their expected toxicity except one bacterium (Enterococcus faecalis). The established assays revealed the concentration dependent onset and intensity of bacterial cytotoxicity and the viability of the cells at 24 h and 48 h exposure.

Conclusion

Impedance measurement and the viability assay Prestoblue™ in combination are suitable as sensitive screening methods to analyze toxic potential of bacteria and can therefor support the risk assessment of workplaces in terms of the directive 2000/54/EC.
The curative effect analysis of a modified Kirschner wires and locking plate internal fixation method for the fifth metacarpal neck fracture
Authors: Gu Song , Zhou Long , Huang Yinjun , Xie Renguo
Published: August 2021

Purpose

To evaluate the efficacy of a modified internal fixation method for the treatment of fifth metacarpal neck fracture.

Methods

From March 2018 to December 2019, 12 patients with the fifth metacarpal neck fractures of the hands were treated with the Kirschner wires and locking plate internal fixation method. Each patient’s gender, age, dominant hand, injured hand, trauma mechanism, preoperative and postoperative deformity (angulation and the length of the fifth metacarpal), the range of motion of the metacarpophalangeal joint and grip strength of each side, the time of return to work, and follow-up time were recorded and calculated.

Results

The mean follow-up time was 16.8 months, and the angulations of preoperative and postoperative deformity were 40.0 ± 3.7°and 17.6 ± 1.7°, respectively. The length of the fifth metacarpals of preoperative and postoperative deformity were 51.5 ± 2.1 mm and 60.0 ± 1.8 mm, respectively. At the last follow-up, the range of motion of the fifth metacarpophalangeal joint of the injured side and the contralateral side were 84.3 ± 3.6°and 86.5 ± 2.0°, and the grip strength of the injured side and the contralateral side were 74.8 ± 6.1 LB and 78.6 ± 8.3 LB, respectively, without statistically significant differences. QDASH score was 2.0 ± 1.0, and the time of return to work was 6.0 ± 0.7 weeks.

Conclusion

The modified internal fixation method is one of the alternative treatments for the fifth metacarpal neck fracture with good curative effects.
Epidemiology and microbiology of fracture-related infection: a multicenter study in Northeast China
Authors: Wang Baisheng , Xiao Xiaoguang , Zhang Jingdong , Han Wenfeng , Hersi Salad Abdirahman , Tang Xin
Published: August 2021

Objective

This study aimed to explore the epidemiological and microbiological characteristics of fracture-related infection (FRI), analyze the drug resistance characteristics of major pathogens, and provide timely and relatively complete clinical and microbiological data for antimicrobial treatment of FRI.

Methods

The clinical and microbiological data of patients with FRI from January 1, 2011, to December 31, 2020, were collected from three tertiary hospitals in Northeast China. The automatic microbial analysis system was used for strain identification and drug susceptibility testing, and the drug susceptibility results were determined in accordance with the latest Clinical and Laboratory Standards Institute (CLSI) criteria (as applicable each year).

Results

A total of 744 patients with FRI were enrolled. The incidence of FRI was about 1.5%, and 81.7% were male patients, with an average age of 48.98 ± 16.01 years. Open fractures accounted for 64.8%. Motor crush (32.8%) and falling (29.8%) were the main causes of injuries. The common sites of infection were the tibia and fibula (47.6%), femur (11.8%), foot (11.8%), and hand (11.6%). A total of 566 pathogenic bacteria were cultured in 378 patients with positive bacterial cultures, of which 53.0% were Gram-positive bacteria and 47.0% were Gram-negative bacteria. The most common pathogen at all sites of infection is Staphylococcus aureus. Staphylococcus aureus had a high resistance rate to penicillin (PEN), erythromycin (ERY), and clindamycin (CLI), exceeding 50%. Methicillin-resistant Staphylococcus aureus (MRSA) was more than 80% resistant to CLI and ERY.

Conclusions

The incidence of FRI in Northeast China was at a low level among major medical centers nationwide. Staphylococcus aureus was still the main pathogen causing bone infections, and the proportion of MRSA was lower than reported abroad, but we have observed an increase in the proportion of infections. Enterobacteriaceae have a higher resistance rate to third-generation cephalosporins and quinolones. For Enterobacteriaceae, other sensitive treatment drugs should be selected clinically.
Evaluation of biomechanical properties on partial and complete epitendinous suture in human cadaver flexor tendon repair
Authors: Kanchanathepsak Thepparat , Wairojanakul Wilarat , Suppaphol Sorasak , Watcharananan Ittirat , Tuntiyatorn Panithan , Tawonsawatruk Tulyapruek
Published: August 2021

Objective

This study was designed to compare the ultimate tensile strength and force to 2 mm gap formation among 50% partial, 75% partial, and complete circumferential epitendinous suture with a combination of 4-strand core suture in human cadaver flexor tendon.

Materials and methods

Forty-five flexor tendons from four soft human cadavers were used to evaluate the biomechanical property among 50% partial, 75% partial, and complete circumferential epitendinous suture with a combination of 4-strand core suture.

Results

The force to 2 mm gap of complete epitendinous was significantly greater than partial epitendinous suture (P < 0.05); however, there was no difference between 50% partial and 75% partial epitendinous suture (P > 0.05). For the ultimate strength, there was no significant difference between partial and complete epitendinous suture (P > 0.05). The partial epitendinous was approximately 60% of the complete epitendinous suture in force to 2 mm gap and also 70% of complete epitendinous suture in ultimate tensile strength with a combination of core sutures.

Conclusions

The complete epitendinous suture showed better ultimate tensile strength and force to 2 mm gap compared with a partial 50% and 75% epitendinous suture. However, in some clinical scenario which the complete epitendinous suture is not possible to perform, the authors suggested only partial epitendinous suture with 50% circumference is recommended as the additional epitendinous repair up 75% circumference cannot provide any mechanical benefit to the repaired site.
Hospital mortality in patients with rare diseases during pandemics: lessons learnt from the COVID-19 and SARS pandemics
Authors: Chung Claudia Ching Yan , Wong Wilfred Hing Sang , Chung Brian Hon Yin
Published: August 2021

Background

The threat and experience of pandemics occur differently for different groups. The rare disease population is at particular risk of being further marginalised during pandemics. In this study, our objective was to assess the hospital mortality patterns in the rare disease and the general populations during the coronavirus disease of 2019 (COVID-19) and severe acute respiratory syndrome (SARS) pandemics in Hong Kong.

Methods

All admission records during the COVID-19 pandemic (January 23–August 23, 2020) and SARS pandemic (March 11–June 30, 2003) were extracted from the local public healthcare database. Patients with rare diseases were identified using one or more of the 1084 10th version International Classification of Diseases and Related Health Problems (ICD-10) codes cross-referenced with 467 ORPHAcodes. Hospital mortality patterns were compared in patients with and without COVID-19/SARS infection. Admission records during the same period in 2019 and 2002 were retrieved for comparison.

Results

During the COVID-19 pandemic, 407,219 patients were admitted to one or more of the 43 public hospitals in Hong Kong, of which, 13,894 were patients with rare diseases (3.4%). A total of 4381 and 77 patients from the general and rare disease populations were infected with COVID-19. Rare disease patients had an adjusted 3.4 times odds of COVID-19-related hospital mortality compared with that of the general population (95% C.I. 1.24–9.41). COVID-19-related mortality was almost exclusively seen in patients ≥ 60 years. While age-related increase in mortality was also observed for the general population during the SARS pandemic, the pattern observed in the rare disease population was significantly different, with a 12.5 times higher SARS-related mortality observed in rare disease patients ≤ 18 years than those in the general population (12.5% vs 1.0%). Patients admitted during the same pandemic periods without coronavirus infection had a significantly higher hospital mortality compared with those admitted one year before the pandemic (p < 0.001).

Conclusion

This population-based study demonstrated the differential impacts of the COVID-19 and SARS pandemics on the rare disease population. In the era of budget and resource scarcity, this study warrants cautious healthcare planning, with consideration of the rare disease population in healthcare prioritisation.
Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
Authors: Bai Bing , Vanderwall David , Li Yuxin , Wang Xusheng , Poudel Suresh , Wang Hong , Dey Kaushik Kumar , Chen Ping-Chung , Yang Ka , Peng Junmin
Published: August 2021

Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer’s disease (AD). Here we review the advances and limitations in historic and recent AD proteomic research. Complementary to genetic mapping, proteomic studies not only validate canonical amyloid and tau pathways, but also uncover novel components in broad protein networks, such as RNA splicing, development, immunity, membrane transport, lipid metabolism, synaptic function, and mitochondrial activity. Meta-analysis of seven deep datasets reveals 2,698 differentially expressed (DE) proteins in the landscape of AD brain proteome (n = 12,017 proteins/genes), covering 35 reported AD genes and risk loci. The DE proteins contain cellular markers enriched in neurons, microglia, astrocytes, oligodendrocytes, and epithelial cells, supporting the involvement of diverse cell types in AD pathology. We discuss the hypothesized protective or detrimental roles of selected DE proteins, emphasizing top proteins in “amyloidome” (all biomolecules in amyloid plaques) and disease progression. Comprehensive PTM analysis represents another layer of molecular events in AD. In particular, tau PTMs are correlated with disease stages and indicate the heterogeneity of individual AD patients. Moreover, the unprecedented proteomic coverage of biofluids, such as cerebrospinal fluid and serum, procures novel putative AD biomarkers through meta-analysis. Thus, proteomics-driven systems biology presents a new frontier to link genotype, proteotype, and phenotype, accelerating the development of improved AD models and treatment strategies.