bluuebunny/crossref_metadata_2025 huggingface dataset:
Segmental artery clamping versus main renal artery clamping in nephron-sparing surgery: updated meta-analysis
Authors: Xu Jinhong , Xu Shuxiong , Yao Biao , Xu Run , Xu Yuangao , Sun Fa , Qiu Qian , Shi Hua
Published: August 2020

Objectives

Ischemia–reperfusion injury is harmful in partial nephrectomy (PN) in renal cell carcinoma. Choosing an appropriate surgical method is important to reduce ischemia–reperfusion injury. This study aimed to compare the effect of segmental artery clamping (SAC) and main renal artery clamping (MAC) on patients who underwent PN.

Methods

Studies from January 2008 to November 2019 were identified by an electronic search of English and Chinese databases, including PubMed, Excerpt Medica Database, Cochrane Library, Wanfang, VIP, and Chinese National Knowledge Internet, without language restriction. Two reviewers were involved in the trial. The effects on operation time (OT), warm ischemia time (WIT), length of hospital stay (LOS), blood transfusion rate, postoperative complication rate, Clavien classification (≥ 3), and positive surgery margin (PSM) were evaluated using Stata software. Standardized mean difference (SMD, for continuous data) and pooled odds ratios (for count data) with 95% confidence interval (CI) were used as effect indicators.

Results

Thirty-two studies were included. SAC decreased the 1-week (SMD = − 0.973; 95% CI = − 1.414, − 0.532;P= 0.000), 1-month (SMD = − 0.411; 95% CI = − 0.769, − 0.053;P= 0.025), and 3-month (affected kidney: SMD = − 0.914; 95% CI = − 1.662, − 0.617;P= 0.000) percentages of postoperative changes in renal function (estimated glomerular filtration rate) between the SAC and MAC groups. Sub-group analysis showed that the SAC group had longer OT (SMD = 0.562; 95% CI = 0.252, 0.871;P= 0.000) than the MAC group. However, no differences were observed in the OT, WIT, LOS, blood transfusion rate, postoperative complication rate, Clavien classification (≥ 3), and PSM between the two groups.

Conclusions

SAC is superior to MAC in terms of short-term postoperative renal function recovery. The use of SAC or MAC depends on tumor size, location, surgical modality, and surgeon’s judgments.
Stage-dependent angiopoietin-Tie2 and nitric oxide signaling of erythrocytes in response to surgical trauma in head and neck cancer
Authors: Wu Hsiang-Ling , Chu You-Hsiang , Tai Ying-Hsuan , Tsou Mei-Yung , Wu Cheng-Hsien , Lo Wen-Liang , Tai Shyh-Kuan , Yeh Chun-Chang , Lu Chih-Cherng
Published: August 2020

Background

Angiopoietin-Tie2 and nitric oxide pathway is crucial in tumor angiogenesis and closely correlates with tumor development, growth, and metastasis. This study aimed to investigate the angiopoietin-Tie2 and nitric oxide signaling of the erythrocyte membrane in response to surgical trauma in head and neck cancer.

Methods

We prospectively enrolled the patients with histology-proven head and neck squamous cell carcinoma undergoing surgical resection of primary tumors at the medical center between August and November 2019. We measured the preoperative and postoperative levels of angiopoietin-1, angiopoietin-2 in plasma using enzyme-linked immunosorbent assays, nitric oxide in plasma using nitrate/nitrite colorimetric assays, and Tie2 phosphorylation in erythrocyte membrane using Western blotting.

Results

The plasma angiopoietin-1 was downregulated from the median 971.3 pg/mL (interquartile range [IQR] 532.1–1569.3) to 417.9 (IQR 270.5–597.3) after tumor resection (p= 0.0020). Conversely, the plasma angiopoietin-2 was enhanced from 1173.6 pg/mL (IQR 977.7–1450.2) to 2353.7 (IQR 1352.4–2954.3) after surgery (p= 0.0021), with a concomitant increase in plasma nitric oxide level from 7.73 μM (IQR 5.39–10.06) to 10.50 (IQR 7.65–14.18) after surgical resection (p= 0.0093). Subgroup analyses further showed the angiopoietin-Tie2 and nitric oxide signaling was significant only in stage III and IV cancer.

Conclusions

The dynamic change of angiopoietin-Tie2 signaling in the erythrocyte membrane along with the enhanced nitric oxide in plasma after tumor resection suggests erythrocytes play a significant role in modulating surgery-induced angiogenesis, which may provide a novel marker for cancer surveillance and control.
A single-center experience with pancreatic cystic neuroendocrine tumors
Authors: Khalil Ange , Ewald Jacques , Marchese Ugo , Autret Aurélie , Garnier Jonathan , Niccoli Patricia , Piana Gilles , Poizat Flora , Giovannini Marc , Delpero Jean-Robert , Turrini Olivier
Published: August 2020

Background

Pancreatic neuroendocrine tumors (PNET) are rare, with a significant malignant potential. This study aimed to determine outcomes of patients with resected PNETs according to the cystic component and confirm the accuracy of preoperative staging.

Methods

From 1997 to 2016, 106 patients underwent resection of PNETs, including 73 purely solid (S-PNETs, 69%), 21 mixed (M-PNETs, 20%), and 12 purely cystic lesions (C-PNETs, 11%). To ensure consistent comparisons of overall (OS) and disease-free (DFS) survival outcomes between the 3 groups, the patients were matched according to the World Health Organization (WHO) grade and tumor height.

Results

Overall, the rate of correlation between the preoperative and pathological diagnoses was low in the C-PNET group (33%, P = 0.03). None of the 24 patients (23%) with metastatic disease at the time of surgery were in the C-PNET group. Furthermore, significantly more parenchyma-sparing resections (P = 0.039) and fewer enlarged resections (P = 0.019) were achieved in the C-PNET group. C-PNET group had a significantly lower node invasion rate than the S-PNET and M-PNET groups (8% vs. 41% and 24%, P = 0.004). Although median OS was comparable in all 3 groups before (P = 0.3) and after (P = 0.18) matching, higher median DFS was observed in the C-PNET group than in the other groups after matching (P = 0.038).

Conclusion

C-PNET was associated with a better prognosis than PNET with a solid component. The results support a wait-and-see policy in cases wherein a reliable preoperative diagnosis remains challenging.
Establishment of a WHO Reference Reagent for anti-Mullerian hormone
Authors: Ferguson Jackie , Hockley Jason , Rigsby Peter , Burns Chris
Published: August 2020

Background

There is a need for a reference material to support the development and ensure the quality of immunoassays for human AMH. A batch of ampoules, coded 16/190, containing lyophilised recombinant AMH was evaluated in a WHO Collaborative Study. The aims of the study were to determine the AMH content in terms of the calibration of each immunoassay method, to predict long-term stability and to assess the suitability of the preparation to calibrate AMH immunoassays.

Methods

Study participants were asked to report the AMH content of specific dilutions of coded ampoules of 16/190 and a comparator preparation containing approximately half the AMH content. In each assay, participants also reported the AMH content of 22 patient samples to assess commutability. A robust all-laboratory geometric mean of the content estimates was determined using the laboratory geometric mean estimates. Commutability was assessed using a difference in bias approach. Stability was predicted by the measurement of thermally accelerated degradation samples.

Results

Seven laboratories performed twenty-one immunoassay method-platform combinations, sixteen of which provided data which met the validity criteria, giving a consensus geometric mean estimate of AMH content of 511 ng/ampoule (95% CI, 426–612, n = 16, GCV 42%) and a robust geometric mean of 489 ng/ampoule. By contrast, the GCV% for the all-laboratory geometric mean of the relative content estimates for the comparator sample to 16/190 was 12%. Commutability was assessed using 20 of the 22 representative patient samples. Of the valid assays, 16/190 was within the limits of acceptable commutability for 6 methods, partially commutable for a further 3 methods and non-commutable when measured by 7 methods. The preparation was predicted to be highly stable when stored at − 20 °C.

Conclusion

The majority of methods met the validity criteria. Content estimates showed a high between-method variability, yet assays exhibited a similar proportionality of response as demonstrated using the comparator sample. 16/190 was commutable in some but not all methods. On the basis of these results, it was agreed by the WHO Expert Committee on Biological Standardization to establish 16/190 as a WHO Reference Reagent for AMH with a content defined by consensus immunoassay of 489 ng/ampoule.
Lactobacillus sakei suppresses collagen-induced arthritis and modulates the differentiation of T helper 17 cells and regulatory B cells
Authors: Jhun Jooyeon , Min Hong Ki , Ryu Jaeyoon , Lee Seon-Yeong , Ryu Jun-Geol , Choi Jeong Won , Na Hyun Sik , Lee Seung Yoon , Jung Yunju , Park Sang-Jun , Park Myeong Soo , Kwon Bin , Ji Geun Eog , Cho Mi-La , Park Sung-Hwan
Published: August 2020

Background

To evaluate the immunomodulatory effect of Lactobacillus sakei in a mouse model of rheumatoid arthritis (RA) and in human immune cells.

Methods

We evaluated whether L. sakei reduced the severity of collagen-induced arthritis (CIA) and modulated interleukin (IL)-17 and IL-10 levels, as well as whether it affected the differentiation of CD4+ T cells and regulatory B cells. We evaluated osteoclastogenesis after culturing bone marrow-derived mononuclear cells with L. sakei.

Results

The differentiation of T helper 17 cells and the serum level of IL-17 were suppressed by L. sakei in both human peripheral blood mononuclear cells and mouse splenocytes. The serum level of IL-10 was significantly increased in the L. sakei-treated group, whereas the regulatory T cell population was unchanged. The population of regulatory B cells significantly increased the in L. sakei-treated group. Oral administration of L. sakei reduced the arthritis incidence and score in mice with CIA. Finally, osteoclastogenesis and the mRNA levels of osteoclast-related genes were suppressed in the L. sakei-treated group.

Conclusion

L. sakei exerted an anti-inflammatory effect in an animal model of RA, regulated Th17 and regulatory B cell differentiation, and suppressed osteoclastogenesis. Our findings suggest that L. sakei has therapeutic potential for RA.
Hemodynamics during the 10-minute NASA Lean Test: evidence of circulatory decompensation in a subset of ME/CFS patients
Authors: Lee Jihyun , Vernon Suzanne D. , Jeys Patricia , Ali Weam , Campos Andrea , Unutmaz Derya , Yellman Brayden , Bateman Lucinda
Published: August 2020

Background

Lightheadedness, fatigue, weakness, heart palpitations, cognitive dysfunction, muscle pain, and exercise intolerance are some of the symptoms of orthostatic intolerance (OI). There is substantial comorbidity of OI in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome). The 10-minute NASA Lean Test (NLT) is a simple, point-of-care method that can aid ME/CFS diagnosis and guide management and treatment of OI. The objective of this study was to understand the hemodynamic changes that occur in ME/CFS patients during the 10-minute NLT.

Methods

A total of 150 ME/CFS patients and 75 age, gender and race matched healthy controls (HCs) were enrolled. We recruited 75 ME/CFS patients who had been sick for less than 4 years (< 4 ME/CFS) and 75 ME/CFS patients sick for more than 10 years (> 10 ME/CFS). The 10-minute NLT involves measurement of blood pressure and heart rate while resting supine and every minute for 10 min while standing with shoulder-blades on the wall for a relaxed stance. Spontaneously reported symptoms are recorded during the test. ANOVA and regression analysis were used to test for differences and relationships in hemodynamics, symptoms and upright activity between groups.

Results

At least 5 min of the 10-minute NLT were required to detect hemodynamic changes. The < 4 ME/CFS group had significantly higher heart rate and abnormally narrowed pulse pressure compared to > 10 ME/CFS and HCs. The < 4 ME/CFS group experienced significantly more OI symptoms compared to > 10 ME/CFS and HCs. The circulatory decompensation observed in the < 4 ME/CFS group was not related to age or medication use.

Conclusions

Circulatory decompensation characterized by increased heart rate and abnormally narrow pulse pressure was identified in a subgroup of ME/CFS patients who have been sick for < 4 years. This suggests inadequate ventricular filling from low venous pressure. The 10-minute NLT can be used to diagnose and treat the circulatory decompensation in this newly recognized subgroup of ME/CFS patients. The > 10 ME/CFS group had less pronounced hemodynamic changes during the NLT possibly from adaptation and compensation that occurs over time. The 10-minute NLT is a simple and clinically useful point-of-care method that can be used for early diagnosis of ME/CFS and help guide OI treatment.
Cancer patients and coronavirus disease 2019: evidence in context
Authors: Barba Maddalena , Krasniqi Eriseld , Ciliberto Gennaro , Vici Patrizia
Published: August 2020

In the rapidly evolving coronavirus disease 2019 (COVID-19) outbreak, inherent literature has been increasing at an impressive rate. Such a dynamic scenario imposes the necessity to define a new framework for cancer care. The first emerging evidence has transmitted contrasting messages with regards to cancer care management. Some authors have hypothesized an increased infection risk for cancer patients, with a more severe disease, requiring a reorganization of health care system that could disrupt an established high quality cancer care routine in many developed countries. Other authors have attempted to interpret data related to cancer patients by better defining their “active status”. We herein present our point of view in the light of current evidence and based on the experience matured at our cancer institute in managing cancer patients during the COVID-19 pandemic. Our core idea is that “active cancer” may be considered a proxy of more recent exposure to diagnostic or therapeutic procedures, and the frequency of access to health care facilities can be predicted as a function of the severity of cancer symptoms. Hence, COVID-19 screening program and the adjustment of cancer care provision in a cancer institutions should be led by this risk model, while awaiting new evidence.
A novel rabbit derived anti-HER2 antibody with pronounced therapeutic effectiveness on HER2-positive breast cancer cells in vitro and in humanized tumor mice (HTM)
Authors: Wege Anja Kathrin , Kirchhammer Nicole , Kazandjian Linda Veronique , Prassl Sandra , Brandt Michael , Piendl Gerhard , Ortmann Olaf , Fischer Stephan , Brockhoff Gero
Published: August 2020

Background

Antibody based cancer therapies have achieved convincing success rates combining enhanced tumor specificity and reduced side effects in patients. Trastuzumab that targets the human epidermal growth factor related receptor 2 (HER2) is one of the greatest success stories in this field. For decades, trastuzumab based treatment regimens are significantly improving the prognosis of HER2-positive breast cancer patients both in the metastatic and the (neo-) adjuvant setting. Nevertheless, ≥ 50% of trastuzumab treated patients experiencede-novoor acquired resistance. Therefore, an enhanced anti-HER2 targeting with improved treatment efficiency is still aspired.

Methods

Here, we determined cellular and molecular mechanisms involved in the treatment of HER2-positive BC cells with a new rabbit derived HER2 specific chimeric monoclonal antibody called “B100″. We evaluated the B100 treatment efficiency of HER2-positive BC cells with different sensitivity to trastuzumab both in vitro and in the presence of a human immune system in humanized tumor mice.

Results

B100 not only efficiently blocks cell proliferation but more importantly induces apoptotic tumor cell death. Detailed in vitro analyses of B100 in comparison to trastuzumab (and pertuzumab) revealed equivalent HER2 internalization and recycling capacity, similar Fc receptor signaling, but different HER2 epitope recognition with high binding and treatment efficiency. In trastuzumab resistant SK-BR-3 based humanized tumor mice the B100 treatment eliminated the primary tumor but even more importantly eradicated metastasized tumor cells in lung, liver, brain, and bone marrow.

Conclusion

Overall, B100 demonstrated an enhanced anti-tumor activity both in vitro and in an enhanced preclinical HTM in vivo model compared to trastuzumab or pertuzumab. Thus, the use of B100 is a promising option to complement and to enhance established treatment regimens for HER2-positive (breast) cancer and to overcome trastuzumab resistance. Extended preclinical analyses using appropriate models and clinical investigations are warranted.
T cell infiltration and upregulation of MHCII in microglia leads to accelerated neuronal loss in an α-synuclein rat model of Parkinson’s disease
Authors: Subbarayan Meena S. , Hudson Charles , Moss Lauren D. , Nash Kevin R. , Bickford Paula C.
Published: August 2020

Background

Parkinson’s disease (PD) is the second most prevalent movement disorder characterized by up to 80% loss of dopamine (DA) neurons and accumulation of Lewy body deposits composed of α-synuclein (α-syn). Accumulation of α-syn is associated with microglial activation, leading to a pro-inflammatory environment linked with the pathogenesis of PD. Along with microglia, CD4 and CD8 T cells are observed in SNpc. The contribution of T-cells to PD development remains unclear with studies demonstrating that they may mediate neurodegeneration or act in a neuroprotective manner.

Methods

Here, we assessed the contribution of T cells to PD neurodegeneration using an adeno-associated virus (AAV) coding human wild-type α-syn or GFP injected into the substantia nigra pars compacta (SNpc) in T cell deficient (athymic nude) and T cell competent (heterozygous) rats. The rats were behaviorally assessed with cylinder test to test paw bias. Following behavior testing, brains were collected and analyzed for markers of dopamine neuron, microglial activation, T cells, and α-syn expression.

Results

Injection of AAV9-α-syn unilaterally into the SN of T cell competent rats resulted in a significant paw bias in comparison to the controls at 60 days post-injection. Conversely, T cell-deficient rats injected with AAV9-α-syn showed no deficit in paw bias. As expected, injected T cell competent rats demonstrated a significant increase in microglial activation (MHCII staining) as well as significant dopaminergic neuron loss. In contrast, the T cell-deficient counterparts did not show a significant increase in microglial activation or significant neuron loss compared to the control animals. We also observed CD4 and CD8 T cells in SNpc following microglial MHCII expression and dopaminergic neuron loss. The time course of T cell entry correlates with upregulation of MHCII and the peak loss of TH+ cells in the SNpc.

Conclusion

These data demonstrate that T cell infiltration and microglial upregulation of MHCII are involved in α-synuclein-mediated DA neuron loss in this rat model of PD.
Sensitivity to temporal parameters of intraneural tactile sensory feedback
Authors: Valle Giacomo , Strauss Ivo , D’Anna Edoardo , Granata Giuseppe , Di Iorio Riccardo , Stieglitz Thomas , Rossini Paolo Maria , Raspopovic Stanisa , Petrini Francesco Maria , Micera Silvestro
Published: August 2020

Background

Recent studies have shown that neural stimulation can be used to provide artificial sensory feedback to amputees eliciting sensations referred on the amputated hand. The temporal properties of the neural stimulation modulate aspects of evoked sensations that can be exploited in a bidirectional hand prosthesis.

Methods

We previously collected evidence that the derivative of the amplitude of the stimulation (intra-digit temporal dynamics) allows subjects to recognize object compliance and that the time delay among stimuli injected through electrodes implanted in different nerves (inter-digit temporal distance) allows to recognize object shapes. Nevertheless, a detailed characterization of the subjects’ sensitivity to variations of intra-digit temporal dynamic and inter-digit temporal distance of the intraneural tactile feedback has not been executed. An exhaustive understanding of the overall potentials and limits of intraneural stimulation to deliver sensory feedback is of paramount importance to bring this approach closer and closer to the natural situation. To this aim, here we asked two trans-radial amputees to identify stimuli with different temporal characteristics delivered to the same active site (intra-digit temporal Dynamic Recognition (DR)) or between two active sites (inter-digit Temporal distance Recognition (TR)). Finally, we compared the results achieved for (simulated) TR with conceptually similar experiments with real objects with one subject.

Results

We found that the subjects were able to identify stimuli with temporal differences (perceptual thresholds) larger than 0.25 s for DR and larger than 0.125 s for TR, respectively. Moreover, we also found no statistically significant differences when the subjects were asked to identify three objects during simulated ‘open-loop’ TR experiments or real ‘closed-loop’ tests while controlling robotic hand.

Conclusions

This study is a new step towards a more detailed analysis of the overall potentials and limits of intraneural sensory feedback. A full characterization is necessary to develop more advanced prostheses capable of restoring all lost functions and of being perceived more as a natural limb by users.
Altered sucking dynamics in a breastfed infant with Down syndrome: a case report
Authors: Coentro Viviane Silva , Geddes Donna T. , Perrella Sharon L.
Published: August 2020

Background

The health and developmental advantages of human milk and breastfeeding are particularly important for infants with Down syndrome. However, they typically have shorter breastfeeding duration due to sucking issues that are not well understood. This case report describes serial measures of milk transfer volumes, sucking dynamics and tongue movement in a breastfeeding infant with Down syndrome. Management of maternal milk production enabled feeding of only breast milk until maturation of breastfeeding skills and the achievement of full breastfeeding by 6 months.

Case presentation

The mother of a term infant with Down syndrome and no associated health complications presented with concerns regarding adequacy of milk removal at the breast and low milk supply. We monitored sucking dynamics during breastfeeding by measuring intraoral vacuum strength, nutritive and non-nutritive suck rates and burst durations, and tongue movement using submental ultrasound. Breastfeeds were monitored at 4, 10, 14, 19 and 24 weeks, and maternal 24 h milk production was measured at 4, 10 and 24 weeks postpartum. We observed a weaker suck strength and shorter nutritive suck duration, and atypical tongue movement up to 19 weeks, with low milk transfer volumes. Regular breast expression was effective in increasing maternal milk production, providing expressed milk for all complementary feeds. Full breastfeeding was achieved by 6 months when reference sucking values were observed.

Conclusions

This case report illustrates that infants with Down syndrome may have low intraoral vacuum and limited nutritive sucking that persists for several months, likely due to delayed oro-motor development. In the absence of effective sucking human milk feeding can continue when milk production is stimulated with frequent and adequate breast expression. It is possible for infants with Down syndrome and no associated health complications to eventually establish full breastfeeding. Mothers that wish to breastfeed their infant with Down syndrome require anticipatory guidance and continuing lactation and family support.
The efficacy of perioperative gabapentin for the treatment of postoperative pain following total knee and hip arthroplasty: a meta-analysis
Authors: Kang Jiayu , Zhao Zhihu , Lv Jianwei , Sun Lei , Lu Bin , Dong Benchao , Ma Jianxiong , Ma Xinlong
Published: August 2020

Background

Postoperative pain after total knee arthroplasty (TKA) and total hip arthroplasty (THA) influence patients’ rehabilitation and life quality. Although gabapentin has been widely used for analgesia, its efficacy is still controversial in TKA and THA. This meta-analysis was performed to assess the efficacy and safety of gabapentin following TKA and THA.

Method

Electronic databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, MEDLINE, and ClinicalTrials.gov were comprehensively retrieved for randomized controlled trials from their inception to June 2019. A total of 7 studies, which compared the administration of gabapentin with that of placebo for the treatment of postoperative pain, were included in our meta-analysis. The meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Result

There was no difference in pain score at 24 (P = 0.87), 48 (P = 0.15), and 72 (P = 0.85) h associated with the use of gabapentin. Likewise, no difference in accumulative morphine consumption at 48 h following TKA or THA was found between gabapentin and placebo (DM = − 8.14, 95% CI − 18.55 to 2.28, P = 0.13). The incidence of opioid-related adverse effects, including nausea, pruritus, sedation, and dizziness, is no difference between gabapentin and placebo group. However, subgroup analysis indicated that gabapentin could reduce the incidence of pruritus after TKA (RR = 0.35, 95% CI 0.12 to 0.99, P = 0.05).

Conclusion

Based on our meta-analysis, gabapentin did not decrease postoperative pain, cumulative morphine consumption, and the incidence of adverse effects after TKA and THA. There was not enough evidence to support the administrations of gabapentin for postoperative pain after TKA and THA.
The role of TDP-43 mislocalization in amyotrophic lateral sclerosis
Authors: Suk Terry R. , Rousseaux Maxime W. C.
Published: August 2020

Since its discovery as a primary component in cytoplasmic aggregates in post-mortem tissue of patients with Amyotrophic Lateral Sclerosis (ALS), TAR DNA Binding Protein 43 kDa (TDP-43) has remained a central focus to understand the disease. TDP-43 links both familial and sporadic forms of ALS as mutations are causative for disease and cytoplasmic aggregates are a hallmark of nearly all cases, regardless of TDP-43 mutational status. Research has focused on the formation and consequences of cytosolic protein aggregates as drivers of ALS pathology through both gain- and loss-of-function mechanisms. Not only does aggregation sequester the normal function of TDP-43, but these aggregates also actively block normal cellular processes inevitably leading to cellular demise in a short time span. Although there may be some benefit to therapeutically targeting TDP-43 aggregation, this step may be too late in disease development to have substantial therapeutic benefit. However, TDP-43 pathology appears to be tightly linked with its mislocalization from the nucleus to the cytoplasm, making it difficult to decouple the consequences of nuclear-to-cytoplasmic mislocalization from protein aggregation. Studies focusing on the effects of TDP-43 mislocalization have demonstrated both gain- and loss-of-function consequences including altered splicing regulation, over responsiveness to cellular stressors, increases in DNA damage, and transcriptome-wide changes. Additionally, mutations inTARDBPconfer a baseline increase in cytoplasmic TDP-43 thus suggesting that small changes in the subcellular localization of TDP-43 could in fact drive early pathology. In this review, we bring forth the theme of protein mislocalization as a key mechanism underlying ALS, by highlighting the importance of maintaining subcellular proteostasis along with the gain- and loss-of-functional consequences when TDP-43 localization is dysregulated. Additional research, focusing on early events in TDP-43 pathogenesis (i.e. to the protein mislocalization stage) will provide insight into disease mechanisms, therapeutic targets, and novel biomarkers for ALS.
TMEM175 mediates Lysosomal function and participates in neuronal injury induced by cerebral ischemia-reperfusion
Authors: Zhang Mengling , Lu Haifeng , Xie Xueshun , Shen Haitao , Li Xiang , Zhang Yunhai , Wu Jiang , Ni Jianqiang , Li Haiying , Chen Gang
Published: August 2020

As the main organelles for the clearance of damaged proteins and damaged organelles, the function of lysosomes is crucial for maintaining the intracellular homeostasis of long-lived neurons. A stable acidic environment is essential for lysosomes to perform their functions. TMEM175 has been identified as a new K+channel that is responsible for regulating lysosomal membrane potential and pH stability in neurons. This study aimed to understand the role of TMEM175 in lysosomal function of neurons and neuronal injury following cerebral ischemia-reperfusion (I/R). A middle-cerebral-artery occlusion/reperfusion (MCAO/R) model was established in adult male Sprague-Dawley rats in vivo, and cultured neurons were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic ischemia-reperfusion (I/R) injury in vitro. We found that the protein level of TMEM175 decreased after cerebral I/R injury and that TMEM175 overexpression ameliorated MCAO/R-induced brain-cell death and neurobehavioral deficits in vivo. Furthermore, these results were recapitulated in cultured neurons. Acridine orange (AO) staining, as well as LysoSensor Green DND-189, cathepsin-B (CTSB), and cathepsin-D (CTSD) activities, showed that TMEM175 deficiency inhibited the hydrolytic function of lysosomes by affecting lysosomal pH. In contrast, TMEM175 upregulation reversed OGD/R-induced lysosomal dysfunction and impaired mitochondrial accumulation in cultured neurons. TMEM175 deficiency induced by cerebral I/R injury leads to compromised lysosomal pH stability, thus inhibiting the hydrolytic function of lysosomes. Consequently, lysosomal-dependent degradation of damaged mitochondria is suppressed and thereby exacerbates brain damage. Exogenous up-regulation of TMEM175 protein level could reverse the neuronal lysosomal dysfunction after ischemia-reperfusion.
A critical role of hippocampus for formation of remote cued fear memory
Authors: Oh Jung-Pyo , Han Jin-Hee
Published: August 2020

A unique feature of fear memory is its persistence that is highly relevant to fear and anxiety-related mental disorders. Recurrent reactivation of neural representations acquired from a traumatic event is thought to contribute to the indelibility of fear memory. Given a well-established role of hippocampus for memory reactivation, hippocampus is likely involved in consolidation process of fear memory. However, evidence suggests that formation of fear memory to a discrete sensory cue is hippocampus-independent. Here, using a pharmacological reversible inactivation of dorsal hippocampus in auditory cued fear conditioning by local infusion of muscimol, we demonstrate in mice that hippocampus is critical for remote memory formation of learned fear to the discrete sensory cue. Muscimol infusion before conditioning did not affect formation of recent auditory fear memory as previously reported. Same muscimol infusion, however, impaired remote auditory fear memory. Muscimol infusion before remote test of auditory fear memory did not affect memory retrieval, indicating hippocampus is not a brain site for storage of remote cued fear memory. Moreover, memory reactivation enforced by re-exposure to the conditioned tone could compensate for hippocampal inactivation, as memory-reactivated mice showed normal remote auditory fear memory despite hippocampal inactivation. Our findings support that hippocampus may have a general role for consolidation of remote associative memory through reactivation of memory trace, giving an insight into how learned fear persists over time.
CircTADA2A suppresses the progression of colorectal cancer via miR-374a-3p/KLF14 axis
Authors: Li Zhen , Yao Hongyu , Wang Shihao , Li Guobin , Gu Xiaoming
Published: August 2020

Background

Colorectal cancer (CRC) is one of the causes of cancer-related death worldwide. The aim of our study was to disclose the expression pattern and underlying molecular mechanism of circular RNA TADA2A (circTADA2A) in CRC.

Methods

The levels of circTADA2A, transcriptional adaptor 2A (TADA2A), microRNA-374a-3p (miR-374a-3p) and Kruppel like factor 14 (KLF14) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Xenograft tumor assay was used to uncover the function of circTADA2A in vivo. The miRNA targets of circTADA2A were searched using circbank and starbase softwares, while DIANA TOOL was used to explore miR-374a-3p-mRNA interactions. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to validate the target relationship of circTADA2A/miR-374a-3p/KLF14 axis. Cell cycle and apoptosis were analyzed by flow cytometry. The glycolysis of CRC cells was determined by Seahorse XFe96 Extracellular Flux Analyzer, Glucose Uptake Colorimetric Assay kit, Lactate Assay Kit II and ATP Colorimetric Assay kit. KLF14 protein level was measured by Western blot assay.

Results

CircTADA2A was abnormally down-regulated in CRC tissues and cell lines. CircTADA2A overexpression impeded CRC tumor growth in vivo. MiR-374a-3p was verified as a target of circTADA2A in CRC cells, and circTADA2A inhibited the malignant potential of CRC cells through targeting miR-374a-3p. MiR-374a-3p interacted with KLF14 messenger RNA (mRNA), and miR-374a-3p deteriorated CRC through down-regulating KLF14. CircTADA2A enhanced the abundance of KLF14 through targeting miR-374a-3p in CRC cells.

Conclusion

CircTADA2A functioned as a tumor suppressor in CRC to inhibit the glycolysis and cell cycle and potentiate the apoptosis of CRC cells via miR-374a-3p/KLF14 axis.
Infant feeding mode predicts the costs of healthcare services in one region of Canada: a data linkage pilot study
Authors: Taylor Alicia , Chowdhury Sharmeen , Gao Zhiwei , Van Nguyen Hai , Midodzi William , Gill Nicole , Halfyard Beth , Newhook Leigh Anne Allwood , Twells Laurie
Published: August 2020

Objective

The aim is to perform a pilot study evaluating the differences in healthcare service use and its associated costs by infant feeding mode in an infant’s first year of life. Data from a prospective cohort study and administrative databases were linked to examine healthcare use in healthy full term infants (N = 160). Exposure was categorized as exclusively breastfed, mixed fed and exclusively formula fed. Outcomes included hospitalizations, emergency room and physician visits. Descriptive statistics and generalized linear modelling were performed.

Results

Overall $315,235 was spent on healthcare service use for the sample of infants during their first year of life. When compared to exclusive breastfeeding, mixed feeding and exclusive formula feeding were found to be significant predictors of total healthcare service use costs (p < 0.05), driven by costs of hospital admissions. Due to the human and economic burden associated with not breastfeeding, policies and programs that support and encourage breastfeeding should be priority.
Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease
Authors: Guo Tengfei , Korman Deniz , La Joie Renaud , Shaw Leslie M. , Trojanowski John Q. , Jagust William J. , Landau Susan M. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2020

Background

Alzheimer’s disease (AD)-related tauopathy can be measured with CSF phosphorylated tau (pTau) and tau PET. We aim to investigate the associations between these measurements and their relative ability to predict subsequent disease progression.

Methods

In 219 cognitively unimpaired and 122 impaired Alzheimer’s Disease Neuroimaging Initiative participants with concurrent amyloid-β (Aβ) PET (18F-florbetapir or18F-florbetaben),18F-flortaucipir (FTP) PET, CSF measurements, structural MRI, and cognition, we examined inter-relationships between these biomarkers and their predictions of subsequent FTP and cognition changes.

Results

The use of a CSF pTau/Aβ40ratio eliminated positive associations we observed between CSF pTau alone and CSF Aβ42in the normal Aβ range likely reflecting individual differences in CSF production rather than pathology. Use of the CSF pTau/Aβ40ratio also increased expected associations with Aβ PET, FTP PET, hippocampal volume, and cognitive decline compared to pTau alone. In Aβ+ individuals, abnormal CSF pTau/Aβ40only individuals (26.7%) were 4 times more prevalent (p <  0.001) than abnormal FTP only individuals (6.8%). Furthermore, among individuals on the AD pathway, CSF pTau/Aβ40mediates the association between Aβ PET and FTP PET accumulation, but FTP PET is more closely linked to subsequent cognitive decline than CSF pTau/Aβ40.

Conclusions

Together, these findings suggest that CSF pTau/Aβ40may be a superior measure of tauopathy compared to CSF pTau alone, and CSF pTau/Aβ40enables detection of tau accumulation at an earlier stage than FTP among Aβ+ individuals.
Treatment strategies for asthma: reshaping the concept of asthma management
Authors: Papi Alberto , Blasi Francesco , Canonica Giorgio Walter , Morandi Luca , Richeldi Luca , Rossi Andrea
Published: August 2020

Asthma is a common chronic disease characterized by episodic or persistent respiratory symptoms and airflow limitation. Asthma treatment is based on a stepwise and control-based approach that involves an iterative cycle of assessment, adjustment of the treatment and review of the response aimed to minimize symptom burden and risk of exacerbations. Anti-inflammatory treatment is the mainstay of asthma management. In this review we will discuss the rationale and barriers to the treatment of asthma that may result in poor outcomes. The benefits of currently available treatments and the possible strategies to overcome the barriers that limit the achievement of asthma control in real-life conditions and how these led to the GINA 2019 guidelines for asthma treatment and prevention will also be discussed.
Duodenal obstruction due to accidental swallowing of a dental prosthesis: a case report and review of the literature
Authors: Mehrabi Saadat , Yavari Barhaghtalab Mohammad Javad , Hosseinpour Reza
Published: August 2020

Background

Artificial dentures are the most common object ingested by elderly patients and account for 4–18% of all foreign body ingestions. Denture impaction in the small bowel is a rare phenomenon. Surgery of the duodenum is difficult, so endoscopy should be the first choice in these patients. There are very rare case reports on denture ingestion-induced duodenal obstruction or perforation, so the aim of this publication was to show a rare case of accidental ingestion of a dental prosthesis with duodenal obstruction and also perforation that could not be treated with endoscopic management and was managed with duodenal kocherization and gastrostomy.

Case presentation

A 47-year-old Iranian woman presented to our hospital with epigastric abdominal pain of 2 hours’ duration after the accidental ingestion of a dental prosthesis 2 days before admission. The patient had severe epigastric tenderness. Radiographic examination revealed nothing. Upper gastrointestinal endoscopy showed a swallowed lodged denture in the second to third parts of the duodenum, and the attempt to extract the denture failed. The patient underwent laparotomy and duodenal kocherization, pushing the denture to the stomach, and gastrostomy, and the denture was brought out without any complications.

Conclusions

Patients with old and worn dentures should have their prosthesis reconstructed and redesigned periodically in order to prevent denture ingestion and its complications. Early surgical intervention is recommended in patients with failed endoscopic extraction of foreign bodies and in those with duodenal perforation.
Patient and health system costs of managing pregnancy and birth-related complications in sub-Saharan Africa: a systematic review
Authors: Mori Amani Thomas , Binyaruka Peter , Hangoma Peter , Robberstad Bjarne , Sandoy Ingvild
Published: August 2020

Background

Morbidity and mortality due to pregnancy and childbearing are high in developing countries. This study aims to estimate patient and health system costs of managing pregnancy and birth-related complications in sub-Saharan Africa.

Methods

A systematic review of the literature was conducted to identify costing studies published and unpublished, from January 2000 to May 2019. The search was done in Pubmed, EMBASE, Cinahl, and Web of Science databases and grey literature. The study was registered in PROSPERO with registration No. CRD42019119316. All costs were converted to 2018 US dollars using relevant Consumer Price Indices.

Results

Out of 1652 studies identified, 48 fulfilled the inclusion criteria. The included studies were of moderate to high quality. Spontaneous vaginal delivery cost patients and health systems between USD 6–52 and USD 8–73, but cesarean section costs between USD 56–377 and USD 80–562, respectively. Patient and health system costs of abortion range between USD 11–66 and USD 40–298, while post-abortion care costs between USD 21–158 and USD 46–151, respectively. The patient and health system costs for managing a case of eclampsia range between USD 52–231 and USD 123–186, while for maternal hemorrhage they range between USD 65–196 and USD 30–127, respectively. Patient cost for caring low-birth weight babies ranges between USD 38–489 while the health system cost was estimated to be USD 514.

Conclusion

This is the first systematic review to compile comprehensive up-to-date patient and health system costs of managing pregnancy and birth-related complications in sub-Saharan Africa. It indicates that these costs are relatively high in this region and that patient costs were largely catastrophic relative to a 10 % of average national per capita income.
Methods for selecting the best evidence to inform a NICE technology appraisal on selective internal radiation therapies for hepatocellular carcinoma
Authors: Wade Ros , Sharif-Hurst Sahar , Harden Melissa , Walton Matthew , Claxton Lindsay , Hodgson Robert , Eastwood Alison
Published: August 2020

Background

Systematic reviews of medical devices are particularly challenging as the quality of evidence tends to be more limited than evidence on pharmaceutical products. This article describes the methods used to identify, select and critically appraise the best available evidence on selective internal radiation therapy devices for treating hepatocellular carcinoma, to inform a technology appraisal for the National Institute for Health and Care Excellence.

Methods

A comprehensive search of ten medical databases and six grey literature sources was undertaken to identify studies of three devices (TheraSphere®, SIR-Spheres® and QuiremSpheres®) for treating hepatocellular carcinoma. The large evidence base was scoped before deciding what level of evidence to include for data extraction and critical appraisal. The methodological quality of the included studies was assessed using criteria relevant to each study design.

Results

Electronic searches identified 4755 records; over 1000 met eligibility criteria after screening titles and abstracts. A hierarchical process was used to scope these records, prioritising comparative studies over non-comparative studies, where available. One hundred ninety-four full papers were ordered; 64 met the eligibility criteria. For each intervention, studies were prioritised by study design and applicability to current UK practice, resulting in 20 studies subjected to critical appraisal and data extraction. Only two trials had a low overall risk of bias. In view of the poor quality of the research evidence, our technology appraisal focused on the two higher quality trials, including a thorough critique of their reliability and generalisability to current UK practice. The 18 poorer quality studies were briefly summarised; many were very small and results were often contradictory. No definitive conclusions could be drawn from the poorer quality research evidence available.

Conclusions

A systematic, pragmatic process was used to select and critically appraise the vast quantity of research evidence available in order to present the most reliable evidence on which to develop recommendations.

Systematic review registration

PROSPERO CRD42019128383.
Agricultural policies, agricultural production and rural households’ welfare in Ethiopia
Authors: Shikur Zewdie Habte
Published: August 2020

The paper employs the computable general equilibrium (CGE) model of the Oromia region of Ethiopia to assess the macroeconomic impacts of agricultural policy on agricultural growth and rural households’ social welfare. The analysis is based on social accounting matrix (SAM) of Oromia region. This Oromia SAM is employed as a framework to estimate the effects of policy shocks on rural households’ social welfare. This SAM provides base year data needed for policy simulation in CGE model of Oromia region. This study develops two simulations based on economic assumptions and tests their effects on agricultural production, and social welfare. The first set of experiment focuses on the irrigation policies that change the factor intensities in the production of agricultural commodities, and the second one focuses on the precision agriculture that raises agricultural productivity in the use of technologies. The analysis identifies that irrigation scaling up has a positive effect on agricultural production, and social welfare. The application of precision agriculture generates a significant and positive effect on agricultural productivity and production, and rural households’ income and consumption. This finding suggests that price support policy should be implemented simultaneously with suggested policies.
Eating disorders among patients with borderline personality disorder: understanding the prevalence and psychopathology
Authors: Khosravi Mohsen
Published: August 2020

Background

Treatment protocols can be bolstered and etiological and maintenance factors can be recognized more easily by a superior understanding of emotions and emotion regulation in the comorbidity of borderline personality disorder (BPD) and feeding and eating disorders (FEDs). Therefore, the present study aimed at investigating the prevalence and psychopathology of FEDs in patients with BPD.

Methods

In this cross-sectional study, 220 participants were examined in three groups, namely BPD (n = 38), BPD + FEDs (n = 72), and healthy controls (n = 110), from August 2018 to November 2019. The participants were selected by systematic random sampling among the patients who referred to Baharan psychiatric hospital in Zahedan, Iran, with the sampling interval of 3. The subjects were evaluated by 28-item General Health Questionnaire (GHQ-28), Borderline Personality Inventory (BPI), Structured Clinical Interview for DSM-5 Personality Disorders (SCID-5-PD), Structured Clinical Interviews for DSM-5: Research Version (SCID-5-RV), the 26-item Eating Attitudes Test (EAT-26), 20-item Toronto Alexithymia Scale (TAS-20), Beck Anxiety Inventory (BAI), and Beck Depression Inventory-II (BDI-II).

Results

The results showed a 65.4% (n = 72) prevalence of FEDs in patients with BPD. Also, the highest and lowest prevalence rates were reported for other specified feeding and eating disorders (51.3%) and bulimia nervosa (6.9%), respectively. Although the highest mean score of TAS-20 was related to anorexia nervosa, there was no significant difference between the scores of various types of FEDs. The mediation analysis showed that anxiety and depression would play a mediating role in the relationship between alexithymia and eating-disordered behaviors.

Conclusions

The results have suggested that alexithymia, anxiety, and depression should receive clinical attention as potential therapeutic targets in the comorbidity of BPD and FEDs. The clinical implications of the research have been conducted to date, and directions for future research have been discussed.