bluuebunny/crossref_metadata_2025 huggingface dataset:
SMART Mental Health Project: process evaluation to understand the barriers and facilitators for implementation of multifaceted intervention in rural India
Authors: Tewari Abha , Kallakuri Sudha , Devarapalli Siddhardha , Peiris David , Patel Anushka , Maulik Pallab K.
Published: February 2021

Background

Globally, mental health problems are a growing public health concern. Resources and services for mental disorders are disproportionately low compared to disease burden. In order to bridge treatment gaps, The Systematic Medical Appraisal, Referral and Treatment (SMART) Mental Health Project was implemented across 12 villages in West Godavari district of the southern Indian state of Andhra Pradesh. This paper reports findings from a process evaluation of feasibility and acceptability of the intervention that focused on a mental health services delivery model to screen, diagnose and manage common mental disorders (CMDs).

Methods

A mixed methods evaluation was undertaken using quantitative service usage analytics, and qualitative data from in-depth interviews and focus group discussions were conducted with stakeholders including primary care physicians, community health workers, field staff and community members. Barriers to and facilitators of intervention implementation were identified. Andersen’s Behavioral Model for Health Services Use was the conceptual framework used to guide the process evaluation and interpretation of data.

Results

In all, 41 Accredited Social Health Activists (ASHAs) and 6 primary health centre (PHC) doctors were trained in mental health symptoms and its management. ASHAs followed up 98.7% of screen positive cases, and 81.2% of these were clinically diagnosed and treated by the PHC doctors. The key facilitators of implementation were adequate training and supervision of field staff, ASHAs and doctors, use of electronic decision support, incorporation of a door-to-door campaign and use of culturally tailored dramas/videos to raise awareness about CMDs, and organising health camps at the village level facilitating delivery of intervention activities. Barriers to implementation included travel distance to receive care, limited knowledge about mental health, high level of stigma related to mental health issues, and poor mobile network signals and connectivity in the villages. Lack of familiarity with and access to mobile phones, especially among women, to accessing health related messages as part of the intervention.

Conclusions

The evaluation not only provides a context to the interventions
delivered, but also allowed an understanding of possible factors that need to
be addressed to make the programme scalable and of benefit to policy makers.
Targeting dopamine receptor D2 as a novel therapeutic strategy in endometrial cancer
Authors: Pierce Stuart R. , Fang Ziwei , Yin Yajie , West Lindsay , Asher Majdouline , Hao Tianran , Zhang Xin , Tucker Katherine , Staley Allison , Fan Yali , Sun Wenchuan , Moore Dominic T. , Xu Chang , Tsai Yi-Hsuan , Parker Joel , Prabhu Varun Vijay , Allen Joshua E. , Lee Douglas , Zhou Chunxiao , Bae-Jump Victoria
Published: February 2021

Background

ONC201 is a dopamine receptor D2 (DRD2) antagonist that inhibits tumor growth in preclinical models through ClpP activation to induce integrated stress response pathway and mitochondrial events related to inhibition of cell growth, which is being explored in clinical trials for solid tumors and hematological malignancies. In this study, we investigated the anti-tumorigenic effect of ONC201 in endometrial cancer cell lines and a genetically engineered mouse model of endometrial cancer.

Methods

Cell proliferation was assessed by MTT and colony formation assays. Cell cycle and apoptosis were evaluated by Cellometer. Invasion capacity was tested using adhesion, transwell and wound healing assays. LKB1fl/flp53fl/fl mouse model of endometrial cancer were fed a control low fat diet versus a high fat diet to mimic diet-induced obesity. Following tumor onset, mice were treated with placebo or ONC201. Metabolomics and lipidomics were used to identify the obesity-dependent effects of ONC201 in the mouse endometrial tumors. DRD2 expression was analyzed by immunohistochemistry in human endometrioid and serous carcinoma specimens. DRD2 mRNA expression from the Cancer Genome Atlas (TCGA) database was compared between the four molecular subtypes of endometrial cancer.

Results

Increasing DRD2 expression in endometrial cancer was significantly associated with grade, serous histology and stage, as well as worse progression free survival and overall survival. Higher expression of DRD2 mRNA was found for the Copy Number High (CNH) subtype when compared to the other subtypes. ONC201 inhibited cell proliferation, induced cell cycle G1 arrest, caused cellular stress and apoptosis and reduced invasion in endometrial cancer cells. Diet-induced obesity promoted endometrial tumor growth while ONC201 exhibited anti-tumorigenic efficacy in the obese and lean LKB1fl/fl/p53fl/fl mice. Metabolomic analysis demonstrated that ONC201 reversed the obesity-driven upregulation of lipid biosynthesis and reduced protein biosynthesis in obese and lean mice.

Conclusion

ONC201 has anti-tumorigenic effects in endometrial cancer cells and a transgenic mouse model of endometrial cancer, and DRD2 expression was documented in both human serous and endometrioid endometrial cancer. These studies support DRD2 antagonism via ONC201 as a promising therapeutic strategy for endometrial cancer that has already demonstrated pharmacodynamic activity and clinical benefit in both serous and endometrioid endometrial cancer patients.
Identification and characterization of neutrophil heterogeneity in sepsis
Authors: Qi Xinxin , Yu Yao , Sun Ran , Huang Jiamin , Liu Lu , Yang Yunxi , Rui Tao , Sun Bingwei
Published: February 2021

Background

Although the immune function of neutrophils in sepsis has been well described, the heterogeneity of neutrophils remains unclear during the process of sepsis.

Methods

In this study, we used a mouse CLP model to simulate the clinical scenario of patients with sepsis, neutrophil infiltration, abnormal distribution and dysfunction was analyzed. LPS was used to stimulate neutrophils in vitro to simulate sepsis; single-cell gene sequencing technology was used to explore the immunological typing. To explore the immunological function of immunosuppressive neutrophils, PD-L1 knockout neutrophils were cocultured with lymphocytes from wild-type mice.

Results

We found that neutrophils presented variant dysfunction at the late stage of sepsis, including inhibition of apoptosis, seriously damaged chemotaxis and extensive infiltration into the tissues. Single-cell RNA sequencing revealed that multiple subclusters of neutrophils were differentiated after LPS stimulation. The two-dimensional spatial distribution analysis showed that Foxp3+ T cells were much closer to Ly-6G than the CD4+ and CD8+ cells, indicating that infiltrated neutrophils may play immunomodulatory effect on surrounding T-regs. Further observations showed that LPS mediates PD-L1 over expression through p38α-MSK1/-MK2 pathway in neutrophils. The subsets of highly expressed PD-L1 exert immunosuppressive effect under direct contact mode, including inhibition of T cell activation and induction of T cell apoptosis and trans-differentiation.

Conclusions

Taken together, our data identify a previously unknown immunosuppressive subset of neutrophils as inhibitory neutrophil in order to more accurately describe the phenotype and characteristics of these cells in sepsis.
Eukaryotic translation factor eIF5A contributes to acetic acid tolerance in Saccharomyces cerevisiae via transcriptional factor Ume6p
Authors: Cheng Yanfei , Zhu Hui , Du Zhengda , Guo Xuena , Zhou Chenyao , Wang Zhaoyue , He Xiuping
Published: February 2021

Background

Saccharomyces cerevisiae is well-known as an ideal model system for basic research and important industrial microorganism for biotechnological applications. Acetic acid is an important growth inhibitor that has deleterious effects on both the growth and fermentation performance of yeast cells. Comprehensive understanding of the mechanisms underlying S. cerevisiae adaptive response to acetic acid is always a focus and indispensable for development of robust industrial strains. eIF5A is a specific translation factor that is especially required for the formation of peptide bond between certain residues including proline regarded as poor substrates for slow peptide bond formation. Decrease of eIF5A activity resulted in temperature-sensitive phenotype of yeast, while up-regulation of eIF5A protected transgenic Arabidopsis against high temperature, oxidative or osmotic stress. However, the exact roles and functional mechanisms of eIF5A in stress response are as yet largely unknown.

Results

In this research, we compared cell growth between the eIF5A overexpressing and the control S. cerevisiae strains under various stressed conditions. Improvement of acetic acid tolerance by enhanced eIF5A activity was observed all in spot assay, growth profiles and survival assay. eIF5A prompts the synthesis of Ume6p, a pleiotropic transcriptional factor containing polyproline motifs, mainly in a translational related way. As a consequence, BEM4, BUD21 and IME4, the direct targets of Ume6p, were up-regulated in eIF5A overexpressing strain, especially under acetic acid stress. Overexpression of UME6 results in similar profiles of cell growth and target genes transcription to eIF5A overexpression, confirming the role of Ume6p and its association between eIF5A and acetic acid tolerance.

Conclusion

Translation factor eIF5A protects yeast cells against acetic acid challenge by the eIF5A-Ume6p-Bud21p/Ime4p/Bem4p axles, which provides new insights into the molecular mechanisms underlying the adaptive response and tolerance to acetic acid in S. cerevisiae and novel targets for construction of robust industrial strains.
Hydrolysis pattern analysis of xylem tissues of woody plants pretreated with hydrogen peroxide and acetic acid: rapid saccharification of softwood for economical bioconversion
Authors: Lee Dae-Seok , Lee Yoon-Gyo , Cho Eun Jin , Song Younho , Bae Hyeun-Jong
Published: February 2021

Background

Woody plants with high glucose content are alternative bioresources for the production of biofuels and biochemicals. Various pretreatment methods may be used to reduce the effects of retardation factors such as lignin interference and cellulose structural recalcitrance on the degradation of the lignocellulose material of woody plants.

Results

A hydrogen peroxide-acetic acid (HPAC) pretreatment was used to reduce the lignin content of several types of woody plants, and the effect of the cellulose structural recalcitrance on the enzymatic hydrolysis was analyzed. The cellulose structural recalcitrance and the degradation patterns of the wood fibers in the xylem tissues ofQuercus acutissima(hardwood) resulted in greater retardation in the enzymatic saccharification than those in the tracheids ofPinus densiflora(softwood). In addition to the HPAC pretreatment, the application of supplementary enzymes (7.5 FPU cellulase for 24 h) further increased the hydrolysis rate ofP. densiflorafrom 61.42 to 91.94% whereas the same effect was not observed forQ. acutissima. It was also observed that endoxylanase synergism significantly affected the hydrolysis ofP. densiflora. However, this synergistic effect was lower for other supplementary enzymes. The maximum concentration of the reducing sugars produced from 10% softwood was 89.17 g L−1after 36 h of hydrolysis with 15 FPU cellulase and other supplementary enzymes. Approximately 80 mg mL−1of reducing sugars was produced with the addition of 7.5 FPU cellulase and other supplementary enzymes after 36 h, achieving rapid saccharification.

Conclusion

HPAC pretreatment removed the interference of lignin, reduced structural recalcitrance of cellulose in theP. densiflora, and enabled rapid saccharification of the woody plants including a high concentration of insoluble substrates with only low amounts of cellulase. HPAC pretreatment may be a viable alternative for the cost-efficient production of biofuels or biochemicals from softwood plant tissues.
Effects of white-tailed deer habitat use preferences on southern cattle fever tick eradication: simulating impact on “pasture vacation” strategies
Authors: Agudelo M. Sofia , Grant William E. , Wang Hsiao‑Hsuan
Published: February 2021

Background

Rhipicephalus (Boophilus) annulatus and Rhipicephalus (Boophilus) microplus (southern cattle fever tick; SCFT), collectively known as cattle-fever ticks (CFTs), are vectors of protozoal parasites (Babesia bigemina and Babesia bovis) that cause bovine babesiosis (also known as cattle fever). One traditional strategy for CFT eradication involves the implementation of a “pasture vacation,” which involves removing cattle (Bos taurus) from an infested pasture for an extended period of time. However, vacated pastures are often inhabited by wildlife hosts, such as white-tailed deer (WTD; Odocoileus virginianus), which can serve as alternate hosts for questing CFTs. We hypothesized that the distribution of host-seeking larvae among habitat types post-pasture vacation would reflect habitat use patterns of WTD, and in turn, affect the subsequent rate of pasture infestation by CFT.

Methods

We adapted a spatially explicit, individual-based model to simulate interactions among SCFT, cattle, and WTD as a tool to investigate the potential effects of WTD habitat use preferences on the efficacy of a pasture vacation. We parameterized the model to represent conditions typical of rangelands in south Texas, USA, simulated a 1-year pasture vacation under different assumptions regarding WTD habitat use preferences, and summarized effects on efficacy through (1) time post-vacation to reach 100% of pre-vacation densities of host-seeking larvae, and (2) the ecological conditions that resulted in the lowest host-seeking larval densities following pasture vacation.

Results

Larval densities at the landscape scale varied seasonally in a similar manner over the entire simulation period, regardless of WTD habitat use preferences. Following the removal of cattle, larval densities declined sharply to < 100 larvae/ha. Following the return of cattle, larval densities increased to > 60% of pre-vacation densities ≈ 21 weeks post-vacation, and reached pre-vacation levels in less than a year. Trends in larval densities in different habitat types paralleled those at the landscape scale over the entire simulation period, but differed quantitatively from one another during the pasture vacation. Relative larval densities (highest to lowest) shifted from (1) wood/shrub, (2) grass, (3) mixed-brush during the pre-vacation period to (1) mixed-brush, (2) wood/shrub, (3) grass or (1) wood/shrub, (2) mixed-brush, (3) grass during the post-vacation period, depending on WTD habitat use preferences.

Conclusions

By monitoring WTD-driven shifts in distributions of SCFT host-seeking larvae among habitat types during simulated pasture vacation experiments, we were able to identify potential SCFT refugia from which recrudescence of infestations could originate. Such information could inform timely applications of acaricides to specific refugia habitats immediately prior to the termination of pasture vacations.

Graphical Abstract
Susceptible trichostrongyloid species mask presence of benzimidazole-resistant Haemonchus contortus in cattle
Authors: Mohammedsalih Khalid M. , Krücken Jürgen , Bashar Ahmed , Juma Fathel-Rahman , Abdalmalaik Abdalhakaim A. H. , Khalafalla Amna , Abakar Adam , Coles Gerald , von Samson-Himmelstjerna Georg
Published: February 2021

Background

Benzimidazole (BZ) anthelmintics are widely used to control infections with parasitic nematodes, but BZ resistance is an emerging threat among several nematode species infecting humans and animals. In Sudan, BZ-resistant Haemonchus contortus populations were recently reported in goats in South Darfur State. The objective of this study was to collect data regarding the situation of BZ resistance in cattle parasitic nematodes in South Darfur using phenotypic and molecular approaches, besides providing some epidemiological data on nematodes in cattle.

Methods

The faecal egg count reduction test and the egg hatch test (EHT) were used to evaluate benzimidazole efficacy in cattle nematodes in five South Darfur study areas: Beleil, Kass, Nyala, Rehed Al-Birdi and Tulus. Genomic DNA was extracted from pools of third-stage larvae (L3) (n = 40) during trials, before and after treatment, and pools of adult male Haemonchus spp. (n = 18) from abattoirs. The polymorphisms F167Y, E198A and F200Y in isotype 1 β-tubulin genes of H. contortus and H. placei were analysed using Sanger and pyrosequencing.

Results

Prevalence of gastro-intestinal helminths in cattle was 71% (313/443). Reduced albendazole faecal egg count reduction efficacy was detected in three study areas: Nyala (93.7%), Rehed Al-Birdi (89.7%) and Tulus (88.2%). In the EHT, EC50 values of these study areas ranged between 0.032 and 0.037 µg/ml thiabendazole. Genus-specific PCRs detected the genera Haemonchus, Trichostrongylus and Cooperia in L3 samples collected after albendazole treatment. Sanger sequencing followed by pyrosequencing assays did not detect elevated frequencies of known BZ resistance-associated alleles in codon F167Y, E198A and F200Y in isotype 1 β-tubulin gene of H. placei (≤ 11.38%). However, polymorphisms were detected in H. contortus and in samples with mixed infections with H. contortus and H. placei at codon 198, including E198L (16/58), E198V (2/58) and potentially E198Stop (1/58). All pooled L3 samples post-albendazole treatment (n = 13) were identified as H. contortus with an E198L substitution at codon 198.

Conclusions

To the knowledge of the authors, this is the first report of reduced albendazole efficacy in cattle in Sudan and is the first study describing an E198L substitution in phenotypically BZ-resistant nematodes collected from cattle.

Graphical Abstract
Molecular characterization and expression analysis of annexin B3 and B38 as secretory proteins in Echinococcus granulosus
Authors: Song Hongyu , He Xue , Du Xiaodi , Hua Ruiqi , Xu Jing , He Ran , Xie Yue , Gu Xiaobin , Peng Xuerong , Yang Guangyou
Published: February 2021

Background

Cystic echinococcosis is a parasitic zoonotic disease, which poses a threat to public health and animal husbandry, and causes significant economic losses. Annexins are a family of phospholipid-binding proteins with calcium ion-binding activity, which have many functions.

Methods

Two annexin protein family genes [Echinococcus granulosus annexin B3 (EgAnxB3) and EgAnxB38] were cloned and molecularly characterized using bioinformatic analysis. The immunoreactivity of recombinant EgAnxB3 (rEgAnxB3) and rEgAnxB38 was investigated using western blotting. The distribution of EgAnxB3 and EgAnxB38 in protoscoleces (PSCs), the germinal layer, 18-day strobilated worms and 45-day adult worms was analyzed by immunofluorescence localization, and their secretory characteristics were analyzed preliminarily; in addition, quantitative real-time reverse transcription polymerase chain reaction was used to analyze their transcript levels in PSCs and 28-day strobilated worms stages. The phospholipid-binding activities of rEgAnxB3 and rEgAnxB38 were also analyzed.

Results

EgAnxB3 and EgAnxB38 are conserved and contain calcium-binding sites. Both rEgAnxB3 and rEgAnxB38 could be specifically recognized by the serum samples from E. granulosus-infected sheep, indicating that they had strong immunoreactivity. EgAnxB3 and EgAnxB38 were distributed in all stages of E. granulosus, and their transcript levels were high in the 28-day strobilated worms. They were found in liver tissues near the cysts. In addition, rEgAnxB3 has Ca2+-dependent phospholipid-binding properties.

Conclusions

EgAnxB3 and EgAnxB38 contain calcium-binding sites, and rEgAnxB3 has Ca2+-dependent phospholipid-binding properties. EgAnxB3 and EgAnxB38 were transcribed in PSCs and 28-day strobilated worms. They were expressed in all stages of E. granulosus, and distributed in the liver tissues near the hydatid cyst, indicating that they are secreted proteins that play a crucial role in the development of E. granulosus.

Graphical Abstract
Anthelmintic efficacy of fenbendazole and levamisole in native fowl in northern Iran
Authors: Saemi Soudkolaei Atefe , Kalidari Gholam Ali , Borji Hassan
Published: February 2021

Background

With the increasing number of free-range domestic chickens, helminth parasites have potentially become more of a threat to commercial flocks in recent years, and routine poultry deworming is needed to improve the efficiency of chicken production. The present study deals with a field trial to study the efficacy of two generally used anthelmintics, fenbendazole and levamisole, against gastrointestinal nematodes of domestic chickens in northern Iran.

Methods

Of 45 domestic chicken flocks involved in the study, 20 flocks were selected to participate in fecal egg count reduction testing based on flock size from April 2017 to September 2018. The infected chickens were randomly divided into three equal groups of 30 each. Ninety chickens in the infected groups received one of the following treatments (d 0 of treatment): Group 1: 5 mg kg−1 body weight (BW) fenbendazole for 3 consecutive days; Group 2: 16 mg kg−1 BW levamisole; Group 3 control: placebo, water + DMSO (dimethylsulfoxide). The efficacy of the treatments was evaluated by comparing fecal egg counts in the treated and control groups.

Results

Examination of three flocks of chickens from the control group showed that 95.0% of the animals were infected with gastrointestinal nematodes with an average geometric value of 361 eggs per gram of feces. Fenbendazole at a dose of 5 mg kg−1 BW for 3 days showed an efficacy of 83.7% (P ≥ 0.05), and levamisole at a dose of 16 mg kg−1 BW showed 71.8% efficacy (P ≥ 0.05) with geometric mean eggs in a gram of feces of 100 and 199.6, respectively. In general, fenbendazole and levamisole treatment led to significantly lower activity. The result of this study revealed that fenbendazole was a better and more effective dewormer than levamisole on the three Iranian domestic chicken flocks, but the difference was not significant. Capillaria spp. were the most generally resistant nematodes followed by Trichostrongylus spp. and Amidostomum anseris.

Conclusion

Our results indicated that fenbendazole and levamisole effectively reduced the number of nemathodes in three Iranian domestic chicken flocks. Given the results of our study, resistance can be expected in the parasitic helminths of poultry. Additional larger scale studies are required to determine the prevalence of anthelmintic resistance in the poultry industry.

Graphical Abstract
The production of excretory-secretory molecules from Heligmosomoides polygyrus bakeri fourth stage larvae varies between mixed and single sex cultures
Authors: Maruszewska-Cheruiyot Marta , Szewczak Ludmiła , Krawczak-Wójcik Katarzyna , Głaczyńska Magdalena , Donskow-Łysoniewska Katarzyna
Published: February 2021

Background

Excretory-secretory (ES) products are crucial in maintaining helminths in the host. Consequently, the proteins of ES are potential vaccine molecules and potential therapeutic agents for autoimmune diseases. Heligmosomoides polygyrus bakeri, a gastrointestinal parasite of mice, is a model of hookworm infection in humans. ES produced by both sexes of H. polygyrus bakeri L4 stage cultured separately shows different immunomodulatory properties than ES obtained when both sexes are cultured together. Accordingly, the objective of this study was to identify and compare the excretory-secretory molecules from single-sex and mixed cultures.

Methods

The composition of ES of male and female L4 stage nematodes in the presence (cultured together) or absence (cultured alone) of the opposite sex was examined. Proteins were identified using mass spectrometry. The functions of identified proteins were explored with Blast2GO.

Results

A total of 258 proteins derived from mixed larval culture in the presence of sex pheromones were identified, 160 proteins from pure female cultures and 172 from pure male cultures. Exposure of nematodes to the sex pheromones results in abundant production of proteins with immunomodulatory properties such as Val proteins, acetylcholinesterases, TGF-β mimic 9 and HpARI. Proteins found only in ES from mixed larval cultures were TGF-β mimics 6 and 7 as well as galectin.

Conclusions

The presence of the opposite sex strongly influences the composition of ES products, probably by chemical (pheromone) communication between individuals. However, examination of the composition of ES from various conditions gives an opportunity for searching for new potentially therapeutic compounds and anthelminthics as well as components of vaccines. Manipulation of the nematode environment might be important for the studies on the immunomodulatory potential of nematodes.

Graphical Abstract
Genetic and functional interaction network analysis reveals global enrichment of regulatory T cell genes influencing basal cell carcinoma susceptibility
Authors: Adolphe Christelle , Xue Angli , Fard Atefeh Taherian , Genovesi Laura A. , Yang Jian , Wainwright Brandon J.
Published: February 2021

Background

Basal cell carcinoma (BCC) of the skin is the most common form of human cancer, with more than 90% of tumours presenting with clear genetic activation of the Hedgehog pathway. However, polygenic risk factors affecting mechanisms such as DNA repair and cell cycle checkpoints or which modulate the tumour microenvironment or host immune system play significant roles in determining whether genetic mutations culminate in BCC development. We set out to define background genetic factors that play a role in influencing BCC susceptibility via promoting or suppressing the effects of oncogenic drivers of BCC.

Methods

We performed genome-wide association studies (GWAS) on 17,416 cases and 375,455 controls. We subsequently performed statistical analysis by integrating data from population-based genetic studies of multi-omics data, including blood- and skin-specific expression quantitative trait loci and methylation quantitative trait loci, thereby defining a list of functionally relevant candidate BCC susceptibility genes from our GWAS loci. We also constructed a local GWAS functional interaction network (consisting of GWAS nearest genes) and another functional interaction network, consisting specifically of candidate BCC susceptibility genes.

Results

A total of 71 GWAS loci and 46 functional candidate BCC susceptibility genes were identified. Increased risk of BCC was associated with the decreased expression of 26 susceptibility genes and increased expression of 20 susceptibility genes. Pathway analysis of the functional candidate gene regulatory network revealed strong enrichment for cell cycle, cell death, and immune regulation processes, with a global enrichment of genes and proteins linked to TReg cell biology.

Conclusions

Our genome-wide association analyses and functional interaction network analysis reveal an enrichment of risk variants that function in an immunosuppressive regulatory network, likely hindering cancer immune surveillance and effective antitumour immunity.
The role of ultrasound imaging in vascular compression syndromes
Authors: Farina Renato , Foti Pietro Valerio , Conti Andrea , Iannace Francesco Aldo , Pennisi Isabella , Fanzone Luigi , Inì Corrado , Libra Federica , Vacirca Francesco , Failla Giovanni , Baldanza Davide , Palmucci Stefano , Santonocito Serafino , Basile Antonio
Published: February 2021

Vascular compression syndromes are rare alterations that have in common the compression of an arterial and/or venous vessel by contiguous structures and can be congenital or acquired. The best known are the Thoracic Outlet Syndrome, Nutcracker Syndrome, May–Thurner Syndrome, and Dunbar Syndrome. The incidence of these pathologies is certainly underestimated due to the non-specific clinical signs and their frequent asymptomaticity. Being a first-level method, Ultrasound plays a very important role in identifying these alterations, almost always allowing a complete diagnostic classification. If in expert hands, this method can significantly contribute to the reduction of false negatives, especially in the asymptomatic population, where the finding of the aforementioned pathologies often happens randomly following routine checks. In this review, we briefly discuss the best known vascular changes, the corresponding ultrasound anatomy, and typical ultrasound patterns.
Effect of resistance training on muscle properties and function in women with generalized joint hypermobility: a single-blind pragmatic randomized controlled trial
Authors: Luder Gere , Aeberli Daniel , Mebes Christine Mueller , Haupt-Bertschy Bettina , Baeyens Jean-Pierre , Verra Martin L.
Published: February 2021

Background

Generalized joint hypermobility is defined as an excessive range of motion in several joints. Having joint hypermobility is not a pathology, but when associated with pain and other symptoms, it might affect health and function. Evidence for physiotherapy management is sparse and resistance training might be a possible intervention. Thus, the effects of 12-week resistance-training on muscle properties and function in women with generalized joint hypermobility were evaluated.

Methods

In this single-blind randomized controlled trial women between 20 and 40 years with generalized joint hypermobility (Beighton score at least 6/9) were included. Participants were randomly allocated to 12-week resistance training twice weekly (experimental) or no lifestyle change (control). Resistance training focused on leg and trunk muscles. Primary outcome was muscle strength; additional outcomes included muscle properties, like muscle mass and density, functional activities, pain and disability. Training adherence and adverse events were recorded.

Results

Of 51 participating women 27 were randomised to training and 24 into the control group. In each group 11 women had joint hypermobility syndrome, fulfilling the Brighton criteria, while 24 (89%) in the training group and 21 (88%) in the control group mentioned any pain. The mean strength of knee extensors varied in the training group from 0.63 (sd 0.16) N/bm before training to 0.64 (sd 0.17) N/bm after training and in the control group from 0.53 (sd 0.14) N/bm to 0.54 (sd 0.15) N/bm. For this and all other outcome measures, no significant differences between the groups due to the intervention were found, with many variables showing high standard deviations. Adherence to the training was good with 63% of participants performing more than 80% of sessions. One adverse event occurred during training, which was not clearly associated to the training. Four participants had to stop the training early.

Conclusions

No improvement in strength or muscle mass by self-guided resistance training was found. Low resistance levels, as well as the choice of outcome measures were possible reasons. A more individualized and better guided training might be important. However, program adherence was good with few side effects or problems triggered by the resistance training.

Trial registration

This trial was prospectively registered in the ISRCTN registry (www.isrctn.com, BMC, Springer Nature) on July 16, 2013 as ISRCTN90224545. The first participant was enrolled at October 25, 2013.
Could dysbiosis of inflammatory and anti-inflammatory gut bacteria have an implications in the development of type 2 diabetes? A pilot investigation
Authors: Kulkarni Prasanna , Devkumar Poornima , Chattopadhyay Indranil
Published: February 2021

Objective

Differential alterations in gut microbiota and chronic low-grade inflammation play a critical role in the development of Type 2 diabetes (T2D). Here we aimed to investigate if dysbiosis of inflammation and anti-inflammation-associated gut bacterial communities in fecal samples of individuals had any influence on T2D using a 16S rRNA gene of V3 region sequencing at Illumina MiSeq platform.

Results

Our findings showed that a higher abundance of inflammatory bacteria such as Lactobacillus ruminis, Ruminococcus gnavus, Bacteroides caccae, Butyricimonas, and Collinsella aerofaciens, and lower abundance of anti-inflammatory bacteria such as Faecalibacterium prausnitzii, and Butyrivibrio that likely play a role in the development of T2D. Our findings hint the potential of indigenous microbiota in developing diagnostic markers and therapeutic targets in T2D.
Bioinformatics analysis of calcium-dependent protein kinase 4 (CDPK4) as Toxoplasma gondii vaccine target
Authors: Foroutan Masoud , Ghaffari Ali Dalir , Soltani Shahrzad , Majidiani Hamidreza , Taghipour Ali , Sabaghan Mohamad
Published: February 2021

Objectives

Toxoplasma gondii(T. gondii), an obligate intracellular apicomplexan parasite, could affect numerous warm-blooded animals, such as humans. Calcium-dependent protein kinases (CDPKs) are essential Ca2+signaling mediators and participate in parasite host cell egress, outer membrane motility, invasion, and cell division.

Results

Several bioinformatics online servers were employed to analyze and predict the important properties of CDPK4 protein. The findings revealed that CDPK4 peptide has 1158 amino acid residues with average molecular weight (MW) of 126.331 KDa. The aliphatic index and GRAVY for this protein were estimated at 66.82 and – 0.650, respectively. The findings revealed that the CDPK4 protein comprised 30.14% and 34.97% alpha-helix, 59.84% and 53.54% random coils, and 10.02% and 11.49% extended strand with SOPMA and GOR4 tools, respectively. Ramachandran plot output showed 87.87%, 8.40%, and 3.73% of amino acid residues in the favored, allowed, and outlier regions, respectively. Also, several potential B and T-cell epitopes were predicted for CDPK4 protein through different bioinformatics tools. Also, antigenicity and allergenicity evaluation demonstrated that this protein has immunogenic and non-allergenic nature. This paper presents a basis for further studies, thereby provides a fundamental basis for the development of an effective vaccine againstT. gondiiinfection.
Acute gastric dilatation in a patient with severe anorexia nervosa: a case report
Authors: Pitre Tyler , Mah Jasmine , Vertes Jaclyn , Tugwell Barna
Published: February 2021

Background

Acute gastric dilatation (AGD) leading to gastric necrosis and perforation has been reported to be a rare but fatal complication in young patients with eating disorders, particularly anorexia nervosa.

Case presentation

We report a case of a Canadian female patient presenting with mild abdominal pain, with a history of anorexia nervosa, the binge/purge subtype, who was found to have severe acute gastric dilatation on subsequent computed tomography imaging. Her clinical course was uncomplicated after gastric decompression. The cause of her AGD was thought to be secondary to dysmotility disorder caused by her anorexia nervosa.

Conclusion

Our case report demonstrates the importance of clinical identification of AGD and subsequent diagnosis and management. Because of the urgency to rule out obstruction or perforation through consultation or additional imaging modalities, recognition and correct diagnosis of this condition is necessary for appropriate patient management. In addition, our case report adds to an underreported but important complication of anorexia nervosa.
Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients
Authors: Liu Fengqiong , Ye Shanliang , Zhu Xin , He Xuesong , Wang Shengzhou , Li Yinbao , Lin Jiang , Wang Jingsu , Lin Yonggan , Ren Xin , Li Yong , Deng Zhaoqun
Published: February 2021

Background

To investigate the potential beneficial effect of fecal microbiota transplantation (FMT) on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients.

Case presentation

A total of 11 COVID-19 patients were recruited in April, 2020, about one month on average after they were discharged from the hospital. All subjects received FMT for 4 consecutive days by oral capsule administrations with 10 capsules for each day. In total, 5 out of 11 patients reported to be suffered from gastrointestinal symptoms, which were improved after FMT. After FMT, alterations of B cells were observed, which was characterized as decreased naive B cell (P = 0.012) and increased memory B cells (P = 0.001) and non-switched B cells (P = 0.012).The microbial community richness indicated by operational taxonomic units number, observed species and Chao1 estimator was marginally increased after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteria (9.2%). FMT can partially restore the gut dysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteria (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium had significantly increased after FMT.

Conclusions

After FMT, altered peripheral lymphocyte subset, restored gut microbiota and alleviated gastrointestinal disorders were observe, suggesting that FMT may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.
Management guidelines for amelogenesis imperfecta: a case report and review of the literature
Authors: Roma M. , Hegde Puneet , Durga Nandhini M. , Hegde Shreya
Published: February 2021

Background

Rehabilitation of the entire dentition with amelogenesis imperfecta (AI) tends to pose a great challenge to the clinician. Most of the cases of amelogenesis imperfecta are reported to be associated with skeletal and dental deformities which results in severe sensitivity of the dental tissues.

Case presentation

This clinical case report marks out the total restoration of the oral condition of a young Indian patient diagnosed with the hypoplastic type of amelogenesis imperfecta. Fixed metal ceramic prosthesis were planned to strengthen the masticatory activity, aesthetics, to banish the dental sensitivity and to build up the general persona of the patient. The patient was followed-up at 6 months, 1 year and 2 years intervals. Functional and esthetic impairment was not visible after the follow up period and the treatment outcome was successful. The entire treatment plan was intended to enhance the functional, esthetic and the masticatory component of the occlusal architecture.

Conclusion

This case report details the presentation, characteristic radiographic findings, and management of a patient with an extremely rare condition of amelogenesis imperfecta.
RETRACTED ARTICLE: MiR-34a inhibitor protects
mesenchymal stem cells from hyperglycaemic injury through the activation of the
SIRT1/FoxO3a autophagy pathway
Authors: Zhang Fengyun , Gao Fei , Wang Kun , Liu Xiaohong , Zhang Zhuoqi
Published: February 2021

Background

Mesenchymal stem cells (MSCs) are favourable treatments for
ischaemic diseases; however, MSCs from diabetic patients are not useful for this
purpose. Recent studies have shown that the expression of miR-34a is
significantly increased in patients with hyperglycaemia; the precise role of
miR-34a in MSCs in diabetes needs to be clarified.

Objective

The aim of this study is to determine the precise role of miR-34a in
MSCs exposed to hyperglycaemia and in recovery heart function after myocardial
infarction (MI) in diabetes mellitus (DM) rats.

Methods

DM rat models were established by high-fat diet combined with
streptozotocin (STZ) injection. MSCs were isolated from the bone marrow of donor
rats. Chronic culture of MSCs under high glucose was used to mimic the DM
micro-environment. The role of miR-34a in regulating cell viability, senescence
and paracrine effects were investigated using a cell counting kit-8 (CCK-8)
assay, senescence-associated β-galactosidase (SA-β-gal) staining and vascular
endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)
ELISA, respectively. The expression of autophagy- and senescence-associated
proteins in MSCs and silent information regulator 1 (SIRT1) and forkhead box
class O 3a (FoxO3a) were analysed by western blotting. Autophagic bodies were
analysed by transmission electron microscopy (TEM). The MI model was established
by left anterior descending coronary artery (LAD) ligation, and then, the rats
were transplanted with differentially treated MSCs intramuscularly at sites
around the border zone of the infarcted heart. Thereafter, cardiac function in
rats in each group was detected via cardiac ultrasonography at 1 week and
3 weeks after surgery. The infarct size was determined through a
2,3,5-triphenyltetrazolium chloride (TTC) staining assay, while myocardial
fibrosis was assessed by Masson staining.

Results

The results of the current study showed that miR-34a was
significantly increased under chronic hyperglycaemia exposure. Overexpression of
miR-34a was significantly associated with impaired cell viability, exacerbated
senescence and disrupted cell paracrine capacity. Moreover, we found that the
mechanism underlying miR-34a-mediated deterioration of MSCs exposed to high
glucose involved the activation of the SIRT1/FoxO3a autophagy pathway. Further
analysis showed that miR-34a inhibitor-treated MSC transplantation could improve
cardiac function and decrease the scar area in DM rats.

Conclusions

Our study demonstrates for the first time that miR-34a mediates the
deterioration of MSCs’ functions under hyperglycaemia. The underlying mechanism
may involve the SIRT1/FoxO3a autophagy signalling pathway. Thus, inhibition of
miR-34a might have important therapeutic implications in MSC-based therapies for
myocardial infarction in DM patients.
Upregulation of IL-15 in the placenta alters trophoblasts behavior contributing to gestational diabetes mellitus
Authors: Li Jiaqi , Li Yuan , Zhou Xuan , Wei Lijie , Zhang Jingyi , Zhu Shenglan , Zhang Huiting , Gao Xuan , Sharifu Lali Mwamaka , Wang Shaoshuai , Xi Ling , Feng Ling
Published: February 2021

Background

Interleukin-15 (IL-15), a member of the ‘four α-helix bundle’ cytokine family, has been associated with many inflammatory and metabolic diseases. Abnormal expression of IL-15 has been linked to the occurrence and development of obesity and diabetes. However, there is a paucity of research on the involvement of IL-15 in Gestational Diabetes Mellitus (GDM). This study aims at investigating the role of IL-15 in the pathogenesis of GDM.

Results

IL-15 was consistently expressed in the placenta throughout pregnancy and dynamically changed with pregnancy progress. Trophoblasts have been identified as the major source of IL-15 in the placenta. Expression of IL-15 was significantly increased in the placenta of GDM and in the trophoblasts cultured with high glucose (HG). In our study, expression of IL-15 in the placenta was positively correlated with blood glucose concentration of 75 g Oral Glucose Tolerance Test (OGTT), and was inversely correlated with weight of newborns. Further investigations in vitro showed that exogenous addition of IL-15 promoted trophoblasts proliferation, improved invasion and tube formation ability by activating the JAK/STAT signaling pathway, which be blocked by JAK inhibitors.

Conclusion

Our results demonstrated that IL-15 expression in the placenta was dynamically changing during pregnancy, and it was upregulated in the placenta of GDM patients. Furthermore, IL-15 altered the biological behavior of trophoblasts through JAK/STAT signaling pathway in vitro, and may contributed to the placental pathology of GDM. Our findings provide a new direction for studying the pathophysiological changes of placenta in GDM.
Predictors of fluid responsiveness in critically ill patients mechanically ventilated at low tidal volumes: systematic review and meta-analysis
Authors: Alvarado Sánchez Jorge Iván , Caicedo Ruiz Juan Daniel , Diaztagle Fernández Juan José , Amaya Zuñiga William Fernando , Ospina-Tascón Gustavo Adolfo , Cruz Martínez Luis Eduardo
Published: February 2021

Introduction

Dynamic predictors of fluid responsiveness have shown good performance in mechanically ventilated patients at tidal volumes (Vt) > 8 mL kg−1. Nevertheless, most critically ill conditions demand lower Vt. We sought to evaluate the operative performance of several predictors of fluid responsiveness at Vt ≤ 8 mL kg−1 by using meta-regression and subgroup analyses.

Methods

A sensitive search was conducted in the Embase and MEDLINE databases. We searched for studies prospectively assessing the operative performance of pulse pressure variation (PPV), stroke volume variation (SVV), end-expiratory occlusion test (EEOT), passive leg raising (PLR), inferior vena cava respiratory variability (Δ-IVC), mini-fluid challenge (m-FC), and tidal volume challenge (VtC), to predict fluid responsiveness in adult patients mechanically ventilated at Vt ≤ 8 ml kg−1, without respiratory effort and arrhythmias, published between 1999 and 2020. Operative performance was assessed using hierarchical and bivariate analyses, while subgroup analysis was used to evaluate variations in their operative performance and sources of heterogeneity. A sensitivity analysis based on the methodological quality of the studies included (QUADAS-2) was also performed.

Results

A total of 33 studies involving 1,352 patients were included for analysis. Areas under the curve (AUC) values for predictors of fluid responsiveness were: for PPV = 0.82, Δ-IVC = 0.86, SVV = 0.90, m-FC = 0.84, PLR = 0.84, EEOT = 0.92, and VtC = 0.92. According to subgroup analyses, variations in methods to measure cardiac output and in turn, to classify patients as responders or non-responders significantly influence the performance of PPV and SVV (p < 0.05). Operative performance of PPV was also significantly affected by the compliance of the respiratory system (p = 0.05), while type of patient (p < 0.01) and thresholds used to determine responsiveness significantly affected the predictability of SVV (p = 0.05). Similarly, volume of fluids infused to determine variation in cardiac output, significantly affected the performance of SVV (p = 0.01) and PLR (p < 0.01). Sensitivity analysis showed no variations in operative performance of PPV (p = 0.39), SVV (p = 0.23) and EEOT (p = 0.15).

Conclusion

Most predictors of fluid responsiveness reliably predict the response of cardiac output to volume expansion in adult patients mechanically ventilated at tidal volumes ≤ 8 ml kg−1. Nevertheless, technical and clinical variables might clearly influence on their operative performance
Efficiency of deep neural networks for joint angle modeling in digital gait assessment
Authors: Conte Alcaraz Javier , Moghaddamnia Sanam , Peissig Jürgen
Published: February 2021

Reliability and user compliance of the applied sensor system are two key issues of digital healthcare and biomedical informatics. For gait assessment applications, accurate joint angle measurements are important. Inertial measurement units (IMUs) have been used in a variety of applications and can also provide significant information on gait kinematics. However, the nonlinear mechanism of human locomotion results in moderate estimation accuracy of the gait kinematics and thus joint angles. To develop “digital twins” as a digital counterpart of body lower limb joint angles, three-dimensional gait kinematic data were collected. This work investigates the estimation accuracy of different neural networks in modeling lower body joint angles in the sagittal plane using the kinematic records of a single IMU attached to the foot. The evaluation results based on the root mean square error (RMSE) show that long short-term memory (LSTM) networks deliver superior performance in nonlinear modeling of the lower limb joint angles compared to other machine learning (ML) approaches. Accordingly, deep learning based on the LSTM architecture is a promising approach in modeling of gait kinematics using a single IMU, and thus can reduce the required physical IMUs attached on the subject and improve the practical application of the sensor system.