bluuebunny/crossref_metadata_2025 huggingface dataset:
A potential association of meditation with menopausal symptoms and blood chemistry in healthy women
Authors: Sung Min-Kyu , Lee Ul Soon , Ha Na Hyun , Koh Eugene , Yang Hyun-Jeong
Published: September 2020

Owing to hormonal changes, women experience various psychophysiological alterations over a wide age range, which may result in decreased quality of life as well as in increased risks of diseases, such as cardiovascular diseases. Although studies have been performed to research complementary methods, such as meditation, the research field still requires an adequate amount of studies for public health guidelines. This pilot cross-sectional study aims to investigate a potential association of meditation with menopausal symptoms and blood chemistry for healthy women. In this study, data of 65 healthy women (age range 25–67) including 33 meditation practitioners and 32 meditation-naïve controls were analyzed to compare the Menopausal Rating Scale scores and blood chemistry with 7 more dropouts in the blood chemistry. For blood chemistry, nine components including glucose (GLU) and high-density lipoprotein cholesterol (HDL) were measured. Two-way analysis of variance was performed by dividing the total participants into 2 groups:premenopausalandpostmenopausalparticipants. Compared to the control group, the meditation group showed a trend of reductions in the Menopausal Rating Scale total score (P = .054) and its 2 subcomponents: depressive mood (P = .064) and irritability (P = .061). In HDL level, there was a significant interaction between group and menopausal state (P = .039) with following post hoc results: among thepremenopausalparticipants, a significant increase in the meditation group compared to the control group (P = .005); among the control group, a significant increase in thepostmenopausalcompared to thepremenopausalparticipants (P = .030). In GLU level, there was a mild interaction between group and menopausal state (P = .070) with following post hoc results: among thepostmenopausalparticipants, a trend of increase in the control group compared to the meditation group (P = .081); among the control group, a significant increase in thepostmenopausalcompared to thepremenopausalparticipants (P = .040). Our research suggests a potential association of practicing meditation with alleviations in menopausal symptoms and changes in blood chemistry, warranting further studies with a longitudinal study design and larger populations to understand the underlying causal relationships.
Morphologic response to chemotherapy containing bevacizumab in patients with colorectal liver metastases
Authors: Hosokawa Ayumu , Yamazaki Kentaro , Matsuda Chu , Ueda Shinya , Kusaba Hitoshi , Okamura Shu , Tsuda Masahiro , Tamura Takao , Shinozaki Katsunori , Tsushima Takahiro , Tsuda Takashi , Shirakawa Tsuyoshi , Yamashita Haruhiro , Morita Satoshi , Hironaka Shuichi , Muro Kei
Published: September 2020

The phase III West Japan Oncology Group (WJOG) 4407G study showed noninferiority of folinic acid, bolus/continuous fluorouracil, and irinotecan plus bevacizumab to modified folinic acid, bolus/continuous fluorouracil, and oxaliplatin 6 plus bevacizumab in progression-free survival (PFS) as first-line chemotherapy for patients with metastatic colorectal cancer. The aim of this study was to evaluate the predictive and prognostic value of morphologic response in patients with colorectal liver metastases (CLM) as a post hoc analysis of the WJOG4407G study.

Morphologic response was assessed by comparing contrast-enhanced computed tomography (CT) images at baseline and week 8. Three blinded radiologists evaluated CT images and classified their response as optimal, incomplete, or no response according to the morphologic criteria. Response evaluation criteria in solid tumors (RECIST) response, early tumor shrinkage (ETS), and depth of response (DpR) were also evaluated.

Among 395 patients who were eligible for efficacy analysis in the WJOG4407G study, 70 patients had liver-limited disease. We finally evaluated 55 of these patients. Optimal morphologic response was identified in 19 of 55 patients (34.5%). The median PFS was 10.7 months for patients with optimal response and 10.1 months in those with incomplete/no response (log-rank, P = .96). The median overall survival (OS) was 26.2 and 35.5 months, respectively (log-rank, P = .062). According to univariate analysis, morphologic response was not associated with PFS or OS, whereas RECIST response was significantly associated with both PFS and OS, with ETS and DpR being associated with significantly longer PFS.

Morphologic response might be neither a predictive nor a prognostic factor in patients with CLM undergoing chemotherapy containing bevacizumab, whereas RECIST response was significantly associated with both PFS and OS.
Nilotinib-induced liver injury
Authors: Tan Youwen , Ye Yun , Zhou Xingbei
Published: September 2020

Introduction:

Nilotinib is a selective inhibitor of the BCR-ABL tyrosine kinase receptor and is used in the management of chronic myelogenous leukemia (CML). Nilotinib therapy at high doses is associated with elevated serum bilirubin levels. If the serum bilirubin level exceeds 3 times the upper limit of normal, the recommendation is to either adjust nilotinib dosage or temporarily discontinue the treatment. However, it is unclear whether hyperbilirubinemia indicates obvious liver histology damage.

Patient concerns:

A 24-year-old man with confirmed CML was treated with nilotinib therapy and developed hyperbilirubinemia after the treatment. Although the first remission of the hyperbilirubinemia was achieved after dose adjustment, the hematological parameters deteriorated. Thus, we initiated an antineoplastic therapy (at the standard dose) until complete remission of the CML was achieved. The pathogenic mechanism of hyperbilirubinemia may be related to the inhibition of uridine diphosphate-glucuronosyltransferase (UGT1A1) activity. Liver histological analysis revealed no significant liver damage. In addition, the patient had no family history of hyperbilirubinemia and liver disease.

Diagnosis:

The patient was admitted to our hospital under the diagnosis of hyperbilirubinemia, and histopathology by liver biopsy showed no obvious damage. We also detected a UGT1A1 mutation [ex1 c.686C > A (p.Pro229Gln)] in the patient and his mother.

Interventions:

When the nilotinib dose was decreased to 300 mg daily, the total bilirubin (TBIL) level decreased to 30 to 50 μmol/L for 1 month. However, because the Bcr-Abl/AblIS ratio did not correspond to the major molecular response (MMR; <0.1%), the nilotinib dose was readjusted to 400 mg daily. One week later, the TBIL and indirect bilirubin levels increased to 89 and 79 μmol/L, respectively. The levels of alanine transaminase and other liver functional indicators were normal.

Outcomes:

A Naranjo Adverse Drug Reaction (ADR) Probability Scale score of 13 indicates that hyperbilirubinemia is attributed to ADR caused by nilotinib rather than by drug-induced liver injury.

Conclusion:

Although reducing the nilotinib dose can alleviate the occurrence of hyperbilirubinemia, the effect of MMR is also reduced. Treatment of CML without dose adjustment or discontinuation of nilotinib therapy may be more advantageous.
The fMRI study for acupuncture on shift work sleep disorder
Authors: Ning Yanzhe , Liu Xueyan , Yao Hao , Chen Pei , Li Xue , Jia Hongxiao
Published: September 2020

Introduction:

Nearly 20% of night shift nurses will cause shift work disorder (SWD) due to the disruption of sleep-wake cycle, which not only affects the daily work efficiency, but also brings a huge burden on physical and mental health. Acupuncture is a safe and effective intervention on SWD. This trial will combine with functional magnetic resonance imaging (fMRI) to study the clinical effects and potential mechanism of acupuncture in the treatment of SWD.

Methods and analysis:

This is a randomized controlled neuroimaging trial, with enrolled participants, outcome assessors, and data statisticians blinded. 60 patients with SWD and 30 healthy controls who sleep regularly will be recruited and divided into divided into a control group, a true acupoints treatment group (TATG) and a sham acupoints treatment group (SATG) by the ratio of 1:1:1. The TATG and SATG will receive 8 sessions of acupuncture treatment in 4 weeks. Cognitive function scales and MRI scanning will be performed before and after 4-week acupuncture treatment. The control group will receive no intervention. Functional connectivity of intra-network and inter-network will be the primary outcome and effect indicator. The secondary outcomes included Repeatable Battery for the Assessment of Neuropsychological Status, Attentional Network Test, Pittsburgh Sleep Quality Index scale and needle sensation assessment scale. Neuroimage indicators will be correlated with clinical data and scores of cognitive function assessment to explore the possible mechanisms underlying the changes of brain activity caused by acupuncture treatment.

Discussion:

The results of this study will enable us to verify the therapeutic effect of acupuncture on SWD and explore the potential central mechanism of acupuncture on SWD from the change of brain activity.
Fast-growing epithelioid hemangioendothelioma of the liver
Authors: Fan Ye-hui , Tang He-nan , Zhou Jian-peng , Fang Qiang , Li Shu-xuan , Kou Kai , Lv Guo-yue
Published: September 2020

Rationale:

Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the liver with malignant potential. It can be of solitary type, multifocal type, or diffuse type. Although there are some characteristic features on radiologic imaging, the definitive diagnosis of HEH is based on histopathology. The surgical treatment of HEH includes liver resection and transplant.

Patient concerns:

A middle-aged woman presented with easy fatiguability and anorexia for 1 month was found to have multifocal lesions on radiological imaging.

Diagnosis:

HEH was diagnosed by needle biopsy. It can be seen from imaging that this case is a multifocal form. The largest lesion increased from 3 to 3.3 cm within 2 months, with an increase of 9.45%; no other relevant literatures have been reported.

Interventions:

The possibility of liver transplantation was suggested to the patient. However, the patient refused transplantation and was successfully treated by radical right hepatectomy and resection of the left lobe lesion.

Outcomes:

She remained disease-free throughout a year follow-up period.

Conclusion:

HEH is a rare disease with characteristic radiological and pathological features. Although liver transplantation is the preferred treatment for multifocal HEH, surgical excision represents one alternative when the lesions can be guaranteed to be completely excised.
Using bioinformatics approach identifies key genes and pathways in idiopathic pulmonary fibrosis
Authors: Xu Zhongbo , Mo Lisha , Feng Xin , Huang Mingru , Li Lin
Published: September 2020

Idiopathic pulmonary fibrosis is a chronic and irreversible respiratory disease with a high incidence worldwide and no specific treatment. Currently, the etiology and pathogenesis of this disease remain largely unknown. In main purpose of this study, bioinformatics analysis was used to uncover key genes and pathways related to idiopathic pulmonary fibrosis (IPF). Gene expression profiles of GSE2052 and GSE35145 were obtained. After combining the 2 chip groups; then, we normalized the data, eliminating batch difference. R software was used to process and to screen differentially expressed genes (DEGs) between the IPF and normal tissues. Then, functional enrichment analysis of these DEGs was carried out, and a protein-protein interaction network (PPI) was also constructed. A total of 276 DEGs (152 up and 134 down-regulated genes) were identified in the IPF lung samples. The PPI network was established with 227 nodes and 763 edges. The top 10 hub genes were CAM1, CDH1, CXCL12, JUN, CTGF, SERPINE1, CXCL1, EDN1, COL1A2, and SPARC. Analyzing the PPI network modules with close interaction, the 3 key modules in the whole PPI network were screened out. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched for the module containing DEGs contained the viral protein interaction with cytokine and the cytokine receptor, the TNF signaling pathway, and the chemokine signaling pathway. The identified key genes and pathways may play an important role in the occurrence and development of IPF, and may be expected to be biomarkers or therapeutic targets for the diagnosis of IPF.
Feasibility of neoadjuvant and adjuvant intraperitoneal chemotherapy in patients with advanced epithelial ovarian cancer
Authors: Liu Yu , Cao Lili , Chen Wei , Wang Jingjing , Wang Wenting , Liang Zhiqing
Published: September 2020

Intraperitoneal (IP) chemotherapy is believed to prolong the survival of patients with advanced ovarian cancer after primary debulking surgery. However, there is little knowledge about IP chemotherapy in the setting of neoadjuvant chemotherapy, and there are contradictory conclusions about adjuvant IP chemotherapy. Here, we evaluated the feasibility of neoadjuvant and adjuvant IP chemotherapy in patients with advanced epithelial ovarian cancer (AEOC).

We retrospectively reviewed the data of 114 patients with AEOC who received neoadjuvant chemotherapy followed by laparoscopic conservative interval debulking surgery (NACT + LIDS) in our institution from January 1, 2009 to December 31, 2017.

The median overall survival (OS) was 56 months and the median disease-free interval (DFI) was 14 months for the entire study population. Neoadjuvant IP chemotherapy cycles were crucial for the treatment of no gross residual (R0) disease (hazard ratio [HR] = 0.446, 95% confidence interval [CI] = 0.245–0.811), which was independently associated with OS of the entire study population (HR = 9.589, 95% CI = 3.911–23.507). In addition, residual disease and body mass index (BMI) were the prognostic factors for DFI (HR = 6.022, 95% CI = 3.632–9.986; HR = 1.085, 95% CI = 1.012–1.163). However, adjuvant IP cycles along with BMI were the determining factors for DFI in the R0 group (HR = 0.703, 95% CI = 0.525–0.941; HR = 1.130, 95% CI = 1.025–1.247), and were associated with OS in the R0 group (HR = 0.488, 95% CI = 0.289–0.824). The OS and DFI Kaplan-Meier curves stratified by adjuvant IP chemothearpy cycles within the R0 group were statistically significant (P = .024 and P = .033, respectively).

Our results showed improvement in patients with AEOC in terms of survival, thus suggesting the feasibility of neoadjuvant and adjuvant IP chemotherapy.
Factors affecting airway compliance and resistance in children receiving general anesthesia during adenotonsillectomy
Authors: Li Jingjie , Li Siyuan , Jiang Hong , Jiang Lai , Qiu Lin
Published: September 2020

Airway compliance is an important index in the surgery of pediatric patients. This study aimed to explore factors affecting dynamic airway compliance (Cdyn) and airway resistance (Raw) after general anesthesia endotracheal intubation for adenotonsillectomy of pediatric patients.

A prospective study was undertaken of 107 children who underwent adenotonsillectomy in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine between January and June 2018. The values of Cdyn and Raw were recorded at 5, 10, and 15 minute during general anesthesia endotracheal intubation. Univariate analysis and multiple linear regression analysis were performed for factors that affected Cdyn and Raw.

Of the 107 patients aged 56.67 ± 18.28 months, 69 (64%) patients were male, and 26 (24%) and 12 (11%) had an upper respiratory infection in the past week and 1 to 2 weeks, respectively. During anesthesia, Cdyn showed a decreasing trend (P < .001) while Raw showed an increasing trend (P < .001). Multivariate analysis revealed that height (β=0.177–0.193) had the strongest correlation with Cdyn; rales during pulmonary auscultation (β= –2.727 to –1.363) and sputum suction (β= –1.670 to –0.949) were also associated with Cdyn (all P < .05). Height was the factor with the strongest negative correlation with Raw (β= –0.382 to –0.305). Rales during pulmonary auscultation (β=10.063–11.326) and sputum suction (β=3.863–9.003) were also associated with Raw (All P < .05).

Height, rales during preoperative auscultation and sputum suction were all associated with intraoperative Cydn and Raw for pediatric patients undergoing adenotonsillectomy and should be considered before the surgery.
“Sclerotic Band” type of classification system and measurement of necrotic area for osteonecrosis of the femoral head
Authors: Zhang Ying , Liu You-Wen , Sun Rui-bo , Fan Yan-nan , Shi Qi-yun , Zhang Lei-Lei , Li Pei-Feng , Li Wu-yin
Published: September 2020

Osteonecrosis of the femoral head is a common orthopedic disease. Based on years of clinical experience and significant imaging data, this study aimed to elucidate a new type of it, to help improve prognosis in young adults and provide a basis for hip preservation treatment.

From January 2014 to December 2016, a total of 211 patients undergoing hip preservation surgery for femoral head necrosis at our hospital were enrolled in this study. Coronal plane classification and cross-sectional area analysis were performed by nuclear magnetic resonance imaging (computed tomography optional) in cases meeting the inclusion criteria. Meanwhile, a new method of classification and calculating the necrotic area was proposed. The application simulation was conducted using sample cases. Additionally, treatment methods were recommended. We used our method to compare the outcome of the selected patients with the JIC classification so as to judge the advantages and disadvantages.

The “ pressure bone trabecular angle ” of the femoral head was measured, and the “sclerotic band” (Zhang Ying) type of classification system and the “quartile” (Zhang Ying) method of measurement were used in 2 sample cases. After analysis, it is more accurate than JIC.

The “Sclerotic band” type of classification system and "quartile" methods are new methods to evaluate the stability of femoral head necrosis. They are convenient for clinical application and easily adopted.
Protocol for a systematic review and meta-analysis of Kang-ai injection for patients with oesophageal cancer
Authors: Song Qingping , Yang Wei , Meng Zhen , Wang Jinyan
Published: September 2020

Background:

Oesophageal cancer (OC) is the sixth leading cause of cancer death worldwide. Despite the improvement of therapeutic methods in recent years, the prognosis of OC remains unsatisfactory. Kang-ai injection, a kind of traditional Chinese herbal medicine, has been widely applied as a promising adjunctive drug for OC. In this study, we aimed to summarize the efficacy and safety of Kang-ai injection for patients with advanced OC through the meta-analysis, in order to provide scientific reference for the design of future clinical trials.

Methods:

Relevant randomized controlled trials and high-quality prospective cohort studies were searched from PubMed, Web of Science, Medline, Cochrane Library, Google Scholar, Excerpt Medica Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Scientific Journal Database and Wanfang Database. Papers in English or Chinese published from their inception to August 2020 will be included without any restrictions.

Study selection and data extraction will be performed independently by 2 investigators. The clinical outcomes including overall response rate, disease control rate, overall survival, disease-free survival, quality of life, immune function and adverse events, were systematically evaluated. Stata 14.0 and Review Manager 5.3 were used for data synthesis, subgroup analysis, sensitivity analysis, meta regression, and risk of bias assessment.

Results:

The results of this study will be published in a peer-reviewed journal, or presented the findings at a relevant conference.

Conclusion:

Our study will draw an objective conclusion of the effects of Kang-ai injection combined with conventional treatment for advanced OC and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for OC patients.

INPLASY registration number:

INPLASY202080019.
Human leukocyte antigen-genotyping according to sex in extrapulmonary tuberculosis patients in Iraq
Authors: Kadhim Hindi Nada Khazal
Published: September 2020

Objective:

The aim of this study was assessment the association of human leukocyte antigen (HLA) alleles and extrapulmonary tuberculosis (EPTB).

Methods:

One-hundred whole blood samples were collected from patients with EPTB (n = 50) and healthy control patients (n = 50). The sequence-specific oligonucleotide was used for HLA-DRB1 genotyping.

Results:

The HLA-DRB1∗7 (relative risk = 4.35) and HLA-DRB1∗3 (relative risk = 3.20) genotypes were significantly more frequent among patients with EPTB compared with healthy subjects (38 vs. 16%, P = 0.002 and 27 vs. 8%, P = 0.002, respectively). The total alleles of the HLA-DRB1 were more common among female patients (60%) vs. male patients (40%). From the result of HLA-DRB1 genotypes, most of the females had two alleles, whereas males mostly had one allele. The frequency of the HLA-DRB1∗3 and HLA-DRB1∗7 was significantly more common in female patients (72 and 62%, respectively), than male patients (28 and 38%, respectively). Moreover, this result was observed for the genotype HLA-DRB1∗15.

Conclusion:

The association of the HLA-DRB1∗3 and the HLA-DRB1∗7 genotypes with the EPTB was observed in this study, albeit needing more verifications. Furthermore, the HLA-DRB1∗315 was more frequent among healthy subjects. More investigations are also essential to confirm the difference between male and female patients with the EPTB regarding the rate of HLA genotypes.
Orbital Osteomyelitis in the Pediatric Patient
Authors: Hu Allison C. , Ng Wendy K.Y.
Published: September 2020

Orbital osteomyelitis in the pediatric patient is a rare clinical entity with limited reports in the literature. Outcomes for orbital osteomyelitis can be potentially fatal, and effective diagnosis and treatment often requires an extensive differential and multidisciplinary team approach. As such, the authors systematically evaluated a pooled analysis of patients in published studies to better understand the clinical trends of this condition. Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement guidelines, the authors queried the PubMed, Cochrane Library, and ISI Web of Science databases. A total of 23 patients (47.8% males) participated in 10 studies between 1977 and 2017. Average age of included patients was 7.3 ± 5.3 years old with follow-up of 8.7 ± 9.8 months. Over half of the patients present with fistula (65.2%) and/or fever (43.5%). Sequestrum formation was common (52.2%) but only seen in chronic osteomyelitis patients. The most frequently infected orbital bone was the frontal bone (n = 10, 43.5%). Nearly all patients were cultured (82.6%) and received imaging, such as computerized tomography (43.5%) or X-ray (47.8%). Streptococcus pyogenes was the most common organism isolated (21.7%), while trauma was the most common source of infection (26.1%). Most patients were treated successfully with combined surgical debridement and antibiotics (73.9%). Significant differences between acute and chronic orbital osteomyelitis patients include clinical presentation, use of magnetic resonance imaging, methicillin-resistant Staphylococcus aureus infection, and procedure only treatments. The studies reviewed here provide a comprehensive overview of the clinical presentation, infection sources, diagnostic modalities, common organisms, and treatment options involved in pediatric orbital osteomyelitis.
Survival Rates and Biomarkers in a Large Animal Model of Traumatic Brain Injury Combined With Two Different Levels of Blood Loss
Authors: Mayer Andrew R. , Dodd Andrew B. , Ling Josef M. , Stephenson David D. , Rannou-Latella Julie G. , Vermillion Meghan S. , Mehos Carissa J. , Johnson Victoria E. , Gigliotti Andrew P. , Dodd Rebecca J. , Chaudry Irshad H. , Meier Timothy B. , Smith Douglas H. , Bragin Denis E. , Lai Chen , Wagner Chelsea L. , Guedes Vivian A. , Gill Jessica M. , Kinsler Rachel
Published: September 2020

Introduction:

The pathology resulting from concurrent traumatic brain injury (TBI) and hemorrhagic shock (HS; TBI+HS) are leading causes of mortality and morbidity worldwide following trauma. However, the majority of large animal models of TBI+HS have utilized focal/contusional injuries rather than incorporating the types of brain trauma (closed-head injury caused by dynamic acceleration) that typify human injury.

Objective:

To examine survival rates and effects on biomarkers from rotational TBI with two levels of HS.

Methods:

Twenty-two sexually mature Yucatan swine (30.39 ± 2.25 kg; 11 females) therefore underwent either Sham trauma procedures (n = 6) or a dynamic acceleration TBI combined with either 55% (n = 8) or 40% (n = 8) blood loss in this serial study.

Results:

Survival rates were significantly higher for the TBI+40% (87.5%) relative to TBI+55% (12.5%) cohort, with the majority of TBI+55% animals expiring within 2 h post-trauma from apnea. Blood-based neural biomarkers and immunohistochemistry indicated evidence of diffuse axonal injury (increased NFL/Aβ42), blood–brain barrier breach (increased immunoglobulin G) and inflammation (increased glial fibrillary acidic protein/ionized calcium-binding adaptor molecule 1) in the injured cohorts relative to Shams. Invasive hemodynamic measurements indicated increased shock index and decreased pulse pressure in both injury cohorts, with evidence of partial recovery for invasive hemodynamic measurements in the TBI+40% cohort. Similarly, although both injury groups demonstrated ionic and blood gas abnormalities immediately postinjury, metabolic acidosis continued to increase in the TBI+55% group ∼85 min postinjury. Somewhat surprisingly, both neural and physiological biomarkers showed significant changes within the Sham cohort across the multi-hour experimental procedure, most likely associated with prolonged anesthesia.

Conclusion:

Current results suggest the TBI+55% model may be more appropriate for severe trauma requiring immediate medical attention/standard fluid resuscitation protocols whereas the TBI+40% model may be useful for studies of prolonged field care.
Gut Microbiota Dysbiosis as a Target for Improved Post-Surgical Outcomes and Improved Patient Care: A Review of Current Literature
Authors: Mustansir Dawoodbhoy Fatema , Patel Bharati Kadamb , Patel Kadamb , Bhatia Madhav , Lee Chuen Neng , Moochhala Shabbir M.
Published: September 2020

Critical illness results in significant changes in the human gut microbiota, leading to the breakdown of the intestinal barrier function, which plays a role in the pathogenesis of multiple organ dysfunction. Patients with sepsis/acute respiratory distress syndrome (ARDS) have a profoundly distorted intestinal microbiota rhythm, which plays a considerable role in the development of gut-derived infections and intestinal dysbiosis. Despite recent medical developments, postsurgical complications are associated with a high morbidity and mortality rate. Bacterial translocation, which is the movement of bacteria and bacterial products across the intestinal barrier, was shown to be a mechanism behind sepsis. Current research is focusing on a solution by addressing significant factors that contribute to intestinal dysbiosis, which subsequently leads to multiple organ failure and, thus, mortality. It may, however, be challenging to manipulate the microbiota in critically ill patients for enhanced therapeutic gain. Probiotic manipulation is advantageous for maintaining the gut–barrier defense and for modulating the immune response. Based on available published research, this review aims to address the application of potential strategies in the intensive care unit, supplemented with current therapeutics by the administration of probiotics, prebiotics, and fecal microbiota transplant, to reduce post-surgical complications of sepsis/ARDS in critically ill patients.
Association Between the Oxygen Consumption: Lactate Ratio and Survival in Critically Ill Patients With Sepsis
Authors: Hoeyer-Nielsen Anne Kirstine , Holmberg Mathias J. , Grossestreuer Anne V. , Yankama Tuyen , Branton Jean-Pierre , Donnino Michael W. , Berg Katherine M.
Published: September 2020

Introduction:

Mitochondrial dysfunction leading to impairment of oxygen extraction, referred to as cytopathic hypoxia, contributes to morbidity in sepsis. Oxygen consumption (VO2) may be a useful measure of the severity of cytopathic hypoxia. We monitored VO2 and carbon dioxide production (VCO2) in septic patients and investigated the association with hospital survival.

Methods:

We retrospectively identified adult (≥18 years) septic patients from a larger prospective observational cohort of critically ill patients on mechanical ventilation. A gas-exchange monitor recorded continuous VO2 and VCO2 for up to 48 h. We then tested the association of median VO2, VCO2, respiratory quotient (RQ), and the VO2:lactate ratio with survival.

Results:

A total of 46 septic patients were included in the analysis, of whom 28 (61%) survived. Overall median VO2 was not associated with survival (3.72 mL/kg/min [IQR: 3.39, 4.92] in survivors and 3.42 mL/kg/min [IQR: 2.97, 5.26] in non-survivors, P = 0.12). The overall median VCO2 and RQ were also not associated with survival. Adjusting for age and the presence of shock did not change these results. The VO2:lactate ratio was associated with survival (adjusted OR 2.17 [95% CI 1.12, 4.22] per unit increase in ratio, P = 0.03). The percent change in median VCO2 was 11.6% [IQR: −8.2, 28.7] in survivors compared with −8.3% [IQR: −18.0, 4.7] in non-survivors (P = 0.03). The percent changes in median VO2 and RQ were not different between groups.

Conclusion:

The VO2:lactate ratio was significantly higher in survivors, while there was no association between median VO2 alone and survival. There was a significant difference in change in VCO2 over time between survivors and non-survivors.
Cognitive flexibility deficits in rats with dorsomedial striatal 6-hydroxydopamine lesions tested using a three-choice serial reaction time task with reversal learning
Authors: Wang Zhuo , Flores Ilse , Donahue Erin K. , Lundquist Adam J. , Guo Yumei , Petzinger Giselle M. , Jakowec Michael W. , Holschneider Daniel P.
Published: September 2020

Lesions of the dorsomedial striatum elicit deficits in cognitive flexibility that are an early feature of Parkinson’s disease (PD), and presumably reflect alterations in frontostriatal processing. The current study aimed to examine deficits in cognitive flexibility in rats with bilateral 6-hydroxydopamine lesions in the dorsomedial striatum. While deficits in cognitive flexibility have previously been examined in rodent PD models using the cross-maze, T-maze, and a food-digging task, the current study is the first to examine such deficits using a 3-choice serial reaction time task (3-CSRT) with reversal learning (3-CSRT-R). Although the rate of acquisition in 3-CSRT was slower in lesioned compared to control rats, lesioned animals were able to acquire a level of accuracy comparable to that of control animals following 4 weeks of training. In contrast, substantial and persistent deficits were apparent during the reversal learning phase. Our results demonstrate that deficits in cognitive flexibility can be robustly unmasked by reversal learning in the 3-CSRT-R paradigm, which can be a useful test for evaluating effects of dorsomedial striatal deafferentation and interventions.
Electroacupuncture at GV24 and bilateral GB13 improves cognitive ability via influences the levels of Aβ, p-tau (s396) and p-tau (s404) in the hippocampus of Alzheimer’s disease model rats
Authors: Yang Yang , Hu Shaowen , Lin Haibo , He Jiang , Tang Chunzhi
Published: September 2020

Acupuncture is widely used to treat various neurodegenerative diseases and can effectively improve cognitive and memory states in Alzheimer’s disease. However, its mechanism is unclear. We speculated that the effect of acupuncture on cognitive function may be associated with reductions in the levels of Aβ and phosphorylated tau in the brain. In this experiment, 60 male Sprague–Dawley rats were randomly divided into control, model, electroacupuncture and nonacupoint groups. We perform electroacupuncture at Shenting (GV24) and bilateral Benshen (GB13) acupoints once a day for 4 weeks in electroacupuncture group (with 1 day of rest after every 6 days of treatment). The electroacupuncture group showed a better performance in cognitive-related behavior tests and significantly lowers the levels of Aβ, p-tau (s396) and p-tau (s404) in the hippocampus. These results may suggest that electroacupuncture at the GV24 and bilateral GB13 acupoints might improve cognitive functions in Alzheimer’s disease by decreasing the levels of Aβ, p-tau (s396) and p-tau (s404) in the brain as these proteins are the main causes of neurological damage and cognitive dysfunction during the pathogenesis underlying Alzheimer’s disease.
Eriodictyol produces antidepressant-like effects and ameliorates cognitive impairments induced by chronic stress
Authors: Zhang Lei , Liu Chen , Yuan Mei
Published: September 2020

Eriodictyol, a natural flavonoid compound identified in numerous medicinal plants, has been reported to have anti-inflammatory, antioxidative and antiproliferative activities and exert protective effects on the neurons, thus drawing attention to its therapeutic potential. However, the effect of eriodictyol on depression remains unclear. In the present study, we investigated the behavioral effects of chronic eriodictyol treatment in rat models of depression induced by lipopolysaccharide (LPS, 1 mg/kg) challenge and chronic unpredictable mild stress (CUMS). We found that chronic eriodictyol (10, 30, and 100 mg/kg) treatment by oral gavage once daily for 14 days dose-dependently produced antidepressant effect in the forced swim test (FST), but did not alter locomotor activity in the open field test. Moreover, oral administration with eriodictyol (100 mg/kg) for 28 days reversed the depressive- and anxiety-like behaviors induced by LPS or CUMS, as evidenced by significantly increased sucrose preference in the sucrose preference test, reduced immobility time in the FST, and reduced latency to feeding in the novelty-suppressed feeding test. In addition, co-administration of subthreshold doses of eriodictyol (30 mg/kg) and transient potential vanilloid 1 receptor antagonist capsazepine (1.5 mg/kg) produced a synergistic effect in these tests. Chronic eriodictyol administration at a dose of 100 mg/kg also rescued the memory deficits induced by CUMS as indicated by the increased exploration index in the novel object recognition test. Altogether, these results demonstrate that eriodictyol attenuates depressive- and anxiety-like behaviors and cognitive impairments in rats, and might be a potential therapeutic avenue for depression.
No, you go first: phenotype and social context affect house sparrow neophobia
Authors: Kelly T. R. , Kimball M. G. , Stansberry K. R. , Lattin C. R.
Published: September 2020

Novel object trials are commonly used to assess aversion to novelty (neophobia), and previous work has shown neophobia can be influenced by the social environment, but whether the altered behaviour persists afterwards (social learning) is largely unknown in wild animals. We assessed house sparrow (Passer domesticus) novel object responses before, during and after being paired with a conspecific of either similar or different behavioural phenotype. During paired trials, animals housed with a similar or more neophobic partner demonstrated an increased aversion to novel objects. This change did not persist a week after unpairing, but neophobia decreased after unpairing in birds previously housed with a less neophobic partner. We also compared novel object responses to non-object control trials to validate our experimental procedure. Our results provide evidence of social learning in a highly successful invasive species, and an interesting asymmetry in the effects of social environment on neophobia behaviour depending on the animal's initial behavioural phenotype.
Zygomorphic flowers have fewer potential pollinator species
Authors: Yoder Jeremy B. , Gomez Giancarlo , Carlson Colin J.
Published: September 2020

Botanists have long identified bilaterally symmetrical (zygomorphic) flowers with more specialized pollination interactions than radially symmetrical (actinomorphic) flowers. Zygomorphic flowers facilitate more precise contact with pollinators, guide pollinator behaviour and exclude less effective pollinators. However, whether zygomorphic flowers are actually visited by a smaller subset of available pollinator species has not been broadly evaluated. We compiled 53 609 floral visitation records in 159 communities and classified the plants' floral symmetry. Globally and within individual communities, plants with zygomorphic flowers are indeed visited by fewer species. At the same time, zygomorphic flowers share a somewhat larger proportion of their visitor species with other co-occurring plants and have particularly high sharing with co-occurring plants that also have zygomorphic flowers. Visitation sub-networks for zygomorphic species also show differences that may arise from reduced visitor diversity, including greater connectance, greater web asymmetry and lower coextinction robustness of both plants and visitor species—but these changes do not necessarily translate to whole plant-visitor communities. These results provide context for widely documented associations between zygomorphy and diversification and imply that species with zygomorphic flowers may face a greater risk of extinction due to pollinator loss.
Sydney Brenner. 13 January 1927—5 April 2019
Authors: White John , Bretscher Mark S.
Published: September 2020

From modest beginnings Sydney became an extraordinarily influential and
accomplished molecular biologist. His critical knowledge of, and insights into,
key scientific problems were legendary. His irrepressible personality, acerbic
wit and ebullient talks inspired a generation of young biologists. He made
seminal discoveries in how genetic information is used for protein synthesis,
and established
Caenorhabditis elegans
as one of the
foremost model organisms for the study of development and neural function. He
also pioneered techniques for genome analysis and was instrumental in
establishing several outstanding centres of biological research around the
world.
The Role of Air Conditioning in the Diffusion of Sars-CoV-2 in Indoor Environments: a First Computational Fluid Dynamic Model, based on Investigations performed at the Vatican State Children’s Hospital
Authors: Borro Luca , Mazzei Lorenzo , Raponi Massimiliano , Piscitelli Prisco , Miani Alessandro , Secinaro Aurelio
Published: September 2020

Background

About 15 million people worldwide were affected by the Sars-Cov-2 infection, which already caused 600,000 deaths. This virus is mainly transmitted through exhalations from the airways of infected persons, so that Heating, Ventilation and Air Conditioning (HVAC) systems might play a role in increasing or reducing the spreading of the infection in indoor environments.

Methods

We modelled the role of HVAC systems in the diffusion of the contagion through Computational Fluid Dynamics (CFD) simulations of cough at the “Bambino Gesù” Vatican State Children’s Hospital.

Both waiting and hospital rooms were modeled as indoor scenarios. A specific Infection-Index (η) parameter was used to estimate the amount of contaminated air inhaled by each person present in the simulated indoor scenarios. The potential role of exhaust air ventilation systems placed above the coughing patient’s mouth was also assessed.

Results

Our CFD-based simulations of the waiting room show that HVAC air-flow remarkably enhances infected droplets diffusion in the whole indoor environment within 25 seconds from the cough event, despite the observed dilution of saliva particles containing the virus. At the same time also their number is reduced due to removal through the HVAC system or deposition on the surfaces. The proper use of Local Exhaust Ventilation systems (LEV) simulated in the hospital room was associated to a complete reduction of infected droplets spreading from the patient’s mouth in the first 0.5 seconds following the cough event. In the hospital room, the use of LEV system completely reduced the η index computed for the patient hospitalized at the bed next to the spreader, with a decreased possibility of contagion.

Conclusions

CFD-based simulations for indoor environment can be useful to optimize air conditioning flow and to predict the contagion risk both in hospitals/ambulatories and in other public/private settings.
Structural and functional connectomes in people with multiple sclerosis
Authors: Tozlu Ceren , Jamison Keith , Gauthier Susan A. , Kuceyeski Amy
Published: September 2020

One of the challenges in multiple sclerosis is that lesion volume does not correlate with symptom severity. Advanced techniques such as diffusion and functional MRI allow imaging of the brain’s connectivity networks, which may provide better insight as to brain-behavior relationships in impairment and compensation in multiple sclerosis. We aim to build machine learning models based on structural and functional connectomes to classify a) healthy controls versus people with multiple sclerosis and b) impaired versus not impaired people with multiple sclerosis. We also aim to identify the most important imaging modality for both classification tasks, and, finally, to investigate which brain regions’ connectome measures contribute most to the classification. Fifteen healthy controls (age=43.6± 8.6, 53% female) and 76 people with multiple sclerosis (age: 45.2 ± 11.4 years, 65% female, disease duration: 12.2 ± 7.2 years) were included. Twenty-three people with multiple sclerosis were considered impaired, with an Expanded Disability Status Scale of 2 or higher. Subjects underwent MRI scans that included anatomical, diffusion and resting-state functional MRI. Random Forest models were constructed using structural and static/dynamic functional connectome measures independently; single modality models were then combined for an ensemble prediction. The accuracy of the models was assessed by the area under the receiver operating curve. Models that included structural connectomes significantly outperformed others when classifying healthy controls and people with multiple sclerosis, having a median accuracy of 0.86 (p-value<0.05, corrected). Models that included dynamic functional connectome metrics significantly outperformed others when distinguishing people with multiple sclerosis by impairment level, having a median accuracy of 0.63 (p-value<0.05, corrected). Structural connectivity between subcortical, somatomotor and visual networks were most damaged by multiple sclerosis. For the classification of patients with multiple sclerosis into impairment severity groups, the most discriminatory metric was dwell time in a dynamic functional connectome state characterized by strong connectivity between and among somatomotor and visual networks. These results suggest that damage to the structural connectome, particularly in the subcortical, visual and somatomotor networks, is a hallmark of multiple sclerosis, and, furthermore, that increased functional coordination between these same regions may be related to severity of motor disability in multiple sclerosis. The use of multi-modal connectome imaging has the potential to shed light on mechanisms of disease and compensation in multiple sclerosis, thus enabling more accurate prognoses and possibly the development of novel therapeutics.
Optimising social mixing strategies to mitigate the impact of COVID-19 in six European countries: a mathematical modelling study
Authors: Ragonnet Romain , Briffoteaux Guillaume , Williams Bridget M. , Savulescu Julian , Segal Matthew , Abayawardana Milinda , Eggo Rosalind M. , Tuyttens Daniel , Melab Nouredine , Marais Ben J. , McBryde Emma S. , Trauer James M.
Published: September 2020

Background

If SARS-CoV-2 elimination is not feasible, strategies are needed to minimise the impact of COVID-19 in the medium-to-long term, until safe and effective vaccines can be used at the population-level.

Methods

Using a mathematical model, we identified contact mitigation strategies that minimised COVID-19-related deaths or years of life lost (YLLs) over a time-horizon of 15 months, using an intervention lasting six or 12 months, in Belgium, France, Italy, Spain, Sweden and the UK. We used strategies that either altered age- or location-specific contact patterns. The optimisation was performed under the constraint that herd immunity should be achieved by the end of the intervention period if post-infection immunity was persistent. We then tested the effect of waning immunity on the strategies.

Findings

Strategies of contact mitigation by age were much more effective than those based on mitigation by location. Extremely stringent contact reductions for individuals aged over 50 were required in most countries to minimise deaths or YLLs. The median final proportion of the population ever-infected with SARS-CoV-2 after herd immunity was reached ranged between 30% and 43%, depending on the country and intervention duration. Compared to an unmitigated scenario, optimised age-specific mitigation was predicted to avert over 1 million deaths across the six countries. The optimised scenarios assuming persistent immunity resulted in comparable hospital occupancies to that experienced during the March-April European wave. However, if immunity was shortlived, high burdens were expected without permanent contact mitigation.

Interpretation

Our analysis suggests that age-selective mitigation strategies can reduce the mortality impacts of COVID-19 dramatically even when significant transmission occurs. The stringency of the required restrictions in some groups raises concerns about the practicality of these strategies. If post-infection immunity was short-lived, solutions based on a mitigation period designed to increase population immunity should be accompanied with ongoing contact mitigation to prevent large epidemic resurgence.
Development of a qualitative real-time RT-PCR assay for the detection of SARS-CoV-2: A guide and case study in setting up an emergency-use, laboratory-developed molecular assay
Authors: Anahtar Melis N. , Shaw Bennett , Slater Damien , Byrne Elizabeth , Botti-Lodovico Yolanda , Adams Gordon , Schaffner Stephen , Eversley Jacqueline , McGrath Graham , Gogakos Tasos , Lennerz Jochen , Marble Hetal Desai , Ritterhouse Lauren L. , Batten Julie , Georgantas N. Zeke , Pellerin Rebecca , Signorelli Sylvia , Thierauf Julia , Kemball Molly , Happi Christian , Grant Donald S. , Ndiaye Daouda , Siddle Katherine J. , Mehta Samar B. , Harris Jason , Ryan Edward T. , Pierce Virginia , LaRocque Regina , Lemieux Jacob E. , Sabeti Pardis , Rosenberg Eric , Branda John , Turbett Sarah E.
Published: September 2020

Developing and deploying new diagnostic tests is difficult, but the need to do so in response to a rapidly emerging pandemic such as COVID-19 is crucially important for an effective response. In the early stages of a pandemic, laboratories play a key role in helping health care providers and public health authorities detect active infection, a task most commonly achieved using nucleic acid-based assays. While the landscape of diagnostics is rapidly evolving, polymerase chain reaction (PCR) remains the gold-standard of nucleic acid-based diagnostic assays, in part due to its reliability, flexibility, and wide deployment. To address a critical local shortage of testing capacity persisting during the COVID-19 outbreak, our hospital set up a molecular based laboratory developed test (LDT) to accurately and safely diagnose SARS-CoV-2. We describe here the process of developing an emergency-use LDT, in the hope that our experience will be useful to other laboratories in future outbreaks and will help to lower barriers to fast and accurate diagnostic testing in crisis conditions.