bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex difference in pulmonary hypertension in the evaluation by exercise echocardiography
Authors: Takase Toru , Taniguchi Mitsugu , Hirano Yutaka , Nakazawa Gaku , Miyazaki Shunichi , Iwanaga Yoshitaka
Published: January 2021

Male patients with pulmonary hypertension have poor survival than their female counterparts. Poor right ventricular function in men may be one of the major determinants of poor prognosis. This study aimed to investigate the difference in hemodynamics during exercise between men and women by exercise echocardiography. Consecutive patients with pulmonary hypertension who underwent right heart catheterization were enrolled, and survival was analyzed. In patients who underwent exercise echocardiography, the change in tricuspid regurgitation pressure gradient during exercise was calculated at multiple stages (low‐, moderate‐, and high‐load exercise), and the mortality was also recorded. In a total of 93 patients, although there were no differences in pulmonary artery pressure and vascular resistance between sexes, male patients showed poor survival. In patients with exercise echocardiography, change in tricuspid regurgitation pressure gradient at low‐load (25 W) exercise was significantly lower in men, although that at maximum‐load exercise was not different between men and women. In the Kaplan–Meier analysis, in a median follow‐up duration of 1760 days, male patients and those with lower change in tricuspid regurgitation pressure gradient at low‐load exercise showed poorer survival (P = 0.002 and 0.026, respectively). In the Cox proportional hazards analysis, the change in tricuspid regurgitation pressure gradient at low‐load exercise was independently associated with poor survival after adjustment for age and sex. In conclusion, a lower change in tricuspid regurgitation pressure gradient at low‐load exercise was observed in male patients and was a prognostic marker, which may be associated, at least in part, with poorer prognosis in male patients with pulmonary hypertension.
Exploring Pre-service Science Teachers’ Perspectives on the Nature of Science: A Comparative Study Between China and Canada
Authors: Zhang (张桂花) Guihua , Li (李远蓉) Yuanrong , Zhou (周国强) George , Ho Sonia Wai-Ying
Published: January 2021

The Nature of Science (NOS) is an important component of scientific literacy. Science teachers’ Views of the Nature of Science (VNOS) directly affect their teaching behaviors. Therefore, it is of great significance to explore science teachers’ VNOS and find ways of improvement. This study was designed to comparatively investigate preservice science teachers’ VNOS between China and Canada. The study employed a survey design to explore how Chinese and Canadian preservice science teachers understood the seven different aspects of NOS. Data showed that preservice science teachers in China and Canada both hold a modern view about science education. The level of Chinese and Canadian participants’ understanding of NOS was above the relatively naive level. Chinese teachers had better macro-understanding toward science education, but their micro-mastery was insufficient. The Canadian participants had a better understanding of the NOS than their Chinese counterparts. The study suggested that there is a need to reconstruct the preservice science teacher education curriculum in China and promote the transformation in the science teacher educational system.
Clinical Importance of Concomitant Cleft Lip/Palate in the Surgical Management of Patients With Congenital Heart Disease
Authors: Toubat Omar , Mallios Demetrios N. , Munabi Naikhoba C. O. , Magee William P. , Starnes Vaughn A. , Kumar S. Ram
Published: January 2021

Background:

Congenital heart disease (CHD) frequently occurs in conjunction with extracardiac developmental anomalies, including cleft malformations. The clinical impact of concomitant cleft disease on the surgical management of CHD has not been studied. We evaluated cardiac surgical outcomes in patients with concomitant CHD and cleft lip and/or palate (CL/P).

Methods:

Patients with CHD + CL/P managed at our institution between January 2004 and December 2018 were included. Demographic, operative, and follow-up data were retrospectively collected and analyzed using SAS 9.4. Chi-square tests were used for categorical variables and t test or Wilcoxon rank sum tests for continuous variables. Significance of P < .05 was used.

Results:

There were 127 patients with CHD + CL/P; 63 (50%) were boys. Compared to the general CHD population, patients with CHD + CL/P demonstrated an enrichment of atrial septal defects (10.5% vs 34%), tetralogy of Fallot/double outlet right ventricle (6.4% vs 15.7%), arch defects (4.5% vs 10.2%), truncus arteriosus (1.2% vs 3.1%), and total anomalous pulmonary venous return (1.0% vs 2.4%). Of 63 patients who underwent CHD repair, 58 (92%) did so prior to CL/P repair at 21.5 (6-114) days of age. Compared to CHD lesion-matched patients undergoing cardiac surgical repair at our institution, patients with CL/P had a 2- to 3.7-fold longer intensive care stay, 1.8- to 2.6-fold longer hospital stay, and 6- to 13.5-fold increase in major morbidity, without a significant difference in mortality.

Conclusions:

Cardiac outflow tract defects are particularly overrepresented in CL/P patients. The presence of CL/P increases the complexity of postoperative care after CHD surgery, without a significant impact on mortality.
Festival or Sport? Chinese Motivations to a Modern Urban Hiking Event
Authors: Chen Fangfang , Naylor Michael , Li Yanning , Dai Shanshan , Ju Peng
Published: January 2021

Festive sport events provide an opportunity for people to engage in leisure in an atmosphere of celebration. It has become increasingly popular in China. Although motivations have been explored thoroughly in the context of participant and recreational sport, events, and festivals, no research has yet focused on the overlap among these domains. To address the gap, this study is an investigation of what motivates people to participate in festive sport events as an emerging subcategory of more traditional events and festivals. After the development of a new motives scale, a questionnaire was administered to 894 participants in a festive sport event for hikers in China. The sample was split in three to validate the scale using factor analysis. Six participant motives in the context of a festive sport event emerged including Physical Health, Achievement, Socialization, Mental Health, Novelty/Excitement, and Culture/Event. Important implications of this study are also discussed.
Urdu Translation and Validation of 11-Item Measure to Assess Borderline Personality Features in Pakistani Adolescents
Authors: Bibi Humaira , Kazmi Syeda Farhana
Published: January 2021

The current study includes Urdu translation and validation of Borderline Personality Features Scale–11 (BPFS-11) in two phases. Phase 1 included forward and back translation of BPFS-11, and Phase 2 included establishment of psychometric properties for BPFS-11. For this purpose, 930 adolescents were selected from different hospitals, schools, and colleges. The reliability value of the scale was .72. Exploratory factor analysis revealed factor structure with four principal dimensions; besides confirmatory factor analysis, goodness-of-fit indices indicated good fit of model to data, and two dimensions of scale and factors showed good values of internal consistency. The obtained value for goodness-of-fit index was .995, for adjusted goodness-of-fit index was .989, for comparative fit index was .998, for incremental fit index was .998, and for root mean square error of approximation (RMSEA) value was .019. Good values of composite reliability and convergent validity were measured for both dimensions of the scale. The analysis of criterion-related validity showed significant positive correlation of BPFS-11 with Affective Lability Scale, Deliberate Self-Harm Inventory, and neuroticism scale of Big Five Inventory. Significant differences were found between scores of individuals having borderline personality disorder and scores of normal individuals. The results of the current study indicated that BPFS-11 is short and easily administered diagnostic tool that has good psychometric properties and can be helpful for diagnosis of borderline personality features in adolescents. It can enhance the understanding of the participants regarding the statements of the scale for Urdu natives.
Athletic Performance in the National Basketball Association After Arthroscopic Debridement of Osteochondral Lesions of the Talus
Authors: Sheu Christopher , Ferkel Richard D.
Published: January 2021

Background:

Use of marrow-stimulating techniques to treat osteochondral lesions of the talus (OLTs) in National Basketball Association (NBA) players is controversial.

Hypothesis:

NBA players will be able to return to preinjury playing status after treatment of OLTs by arthroscopic debridement alone without marrow-stimulating techniques.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Between the 2000 and 2015 seasons, 10 NBA players were treated with arthroscopic debridement of an OLT. The following performance outcomes were compared pre- and postoperatively: seasons played, games played, games started, minutes per game, points per game, field goals, 3-point shots, rebounds, assists, double doubles, triple doubles, steals, blocks, turnovers, personal fouls, assists per turnovers, steals per turnovers, NBA rating, scoring efficiency, and shooting efficiency. In addition, the players were compared with a matched control group using mixed effects regression and Fisher least significant difference modeling.

Results:

All 10 players returned to play in the NBA after arthroscopic debridement without microfracture or drilling of an OLT. When compared with preoperative performance, postoperative mean points scored, assists made, and steals made increased by 2.86 ( P = .042), 0.61 ( P = .049), and 0.15 ( P = .027), respectively. Only field goal percentage decreased postoperatively when compared with matched controls; however, this normalized by the end of the second season after surgery. There was no statistically significant change in any of the other performance factors when compared with matched controls. All patients returned to basketball during the same season (n = 1) or the following season (n = 9) if the operation was performed off-season. The mean length of career after surgery was 4.1 years, with 5 players still playing in the league at the time of this study.

Conclusion:

After arthroscopic debridement of an OLT without drilling or microfracture, there was a high rate of return to the NBA, with improved points scored, assists, and steals made after surgery when compared with preoperative performance. There was no statistically significant change in any performance factors when compared with uninjured matched controls. Lesion size did not affect player career length. These data should be used to manage patients’ and teams’ expectations regarding players’ ability to return to elite levels of athletic performance after surgery of an OLT.
Displacing the Anthropocene: Colonisation, extinction and the unruliness of nature in Palestine
Authors: Salih Ruba , Corry Olaf
Published: January 2021

Recent ‘Anthropocene’ commentaries have argued that as humans have become decisively entangled in natural systems, they collectively became a geological species-agent potentially becoming aware of its own place in the deep history of planetary time. Through this, the argument goes, a pre-political collective consciousness could emerge, paving the way for a progressive construction of a common world, beyond particularistic justice-claims. The reverse case is made in scholarship of settler colonialism: the Anthropocene is rooted in histories of settler colonial violence and is deeply tied up with the dispossession and ‘extinction’ of Indigenous life-worlds. In this article, we foreground nature–human entanglement as crucial for understanding the operations but also the instability of settler colonialism in Palestine. We suggest that fractures and openings become legible when paying attention to the ‘afterlife’ of nature that was erased due to its enmeshment with Indigenous people. We provide a historical and ethnographic account of past and emerging entanglements between Palestinians refugees and their nature, ultimately arguing that indigeneity is recalcitrant to obliteration. With that in mind, we return to the Anthropocene’s focus on universal human extinction and ethical consciousness by critically engaging with it from the standpoint of colonised and displaced Indigenous populations, like the Palestinian refugees. We conclude by arguing that only when the profoundly unequal access to Life entrenched in settler colonialism is foregrounded and addressed, does a real possibility of recognising any common, global vulnerability that the species faces emerge.
What Explains FDI Inflows to ASEAN Countries? Evidence from Quantile Regressions
Authors: Sahu Jagadish Prasad , Dash Santosh Kumar
Published: January 2021

This article examines the determinants of foreign direct investment (FDI) inflows to five economies of the Association of Southeast Asian Nations (ASEAN) for the period 1985–2017. Using the fixed effects quantile regression (QR) method, we identify the differential effects of the covariates across the conditional distribution of FDI inflows. The results suggest that financial sector development and natural resources in the host country are the most significant determinants of FDI inflows to the ASEAN region. Financial sector development is significant at both higher and lower quantiles of the distribution of FDI inflows, whereas natural resources and political regime are significant at the upper quantiles. The findings suggest that while financial sector development is an important factor for attracting FDI, natural resources and political regime matter for large inflows of FDI to the ASEAN countries. The article concludes that the resource-seeking and the efficiency-seeking motives of the multinational corporations are the primary reasons of large inflows of FDI to the ASEAN countries.
Plasma levels of von Willebrand factor and future risk of incident venous thromboembolism
Authors: Edvardsen Magnus S. , Hindberg Kristian , Hansen Ellen-Sofie , Morelli Vânia M. , Ueland Thor , Aukrust Pål , Brækkan Sigrid K. , Evensen Line H. , Hansen John-Bjarne
Published: January 2021

Several case-control studies have reported elevated plasma von Willebrand factor (VWF) levels in patients with venous thromboembolism (VTE) compared with controls. However, because few studies have investigated the association in a prospective design, it is unclear whether elevated plasma VWF is a risk factor or a consequence of the VTE event. Therefore, we aimed to investigate the prospective association between plasma VWF levels and risk of VTE, as well as to perform subgroup analyses of deep vein thrombosis (DVT) and pulmonary embolism. We established a population-based nested case-control study of 414 VTE cases and 843 age- and sex-matched controls based on the Tromsø study cohort (1994-2007). Blood samples were collected at cohort baseline (1994-1995). Odds ratios (ORs) with 95% confidence intervals (CIs) for VTE were estimated across quartiles of VWF levels. We found that the risk of VTE increased linearly across quartiles of VWF levels (P for trend = .023). Participants with VWF in the highest quartile had an OR of 1.45 (95% CI, 1.03-2.03) for VTE compared with those in the lowest quartile. The association was strongest for unprovoked VTE (OR, 2.74; 95% CI, 1.66-4.54) and unprovoked DVT in particular (OR, 6.73; 95% CI, 3.07-14.76). Further adjustment for body mass index, C-reactive protein, hypertension, estrogen use, and smoking had a modest effect on the risk estimates. To conclude, we found a dose-dependent relationship between plasma VWF levels and future risk of incident VTE, and unprovoked events in particular. Our findings suggest that VWF may represent a promising biomarker for future risk of incident VTE.
Facing the needs for clean bicycle data – a bicycle-specific approach of GPS data processing
Authors: Lißner Sven , Huber Stefan
Published: January 2021

Background

GPS-based cycling data are increasingly available for traffic planning these days. However, the recorded data often contain more information than simply bicycle trips. GPS tracks resulting from tracking while using other modes of transport than bike or long periods at working locations while people are still tracking are only some examples. Thus, collected bicycle GPS data need to be processed adequately to use them for transportation planning.

Results

The article presents a multi-level approach towards bicycle-specific data processing. The data processing model contains different steps of processing (data filtering, smoothing, trip segmentation, transport mode recognition, driving mode detection) to finally obtain a correct data set that contains bicycle trips, only. The validation reveals a sound accuracy of the model at its’ current state (82–88%).
Decomposition of gender differences in cognitive functioning: National Survey of the Japanese elderly
Authors: Okamoto Shohei , Kobayashi Erika , Murayama Hiroshi , Liang Jersey , Fukaya Taro , Shinkai Shoji
Published: January 2021

Background

It is well known that females generally live longer than males, but women tend to suffer from more illnesses and limitations than men do, also for dementia. However, limited empirical evidence is available why this ‘male-female health-survival paradox’ is observed. This study aimed to investigate factors which account for gender differences in health, particularly cognitive functioning and decline among older adults.

Methods

Data were retrieved from the National Survey of the Japanese Elderly, which is a longitudinal survey of a nationwide representative sample of Japanese adults aged 60 or over. Gender differences in cognitive functioning and decline in three-year follow-ups were decomposed using Blinder–Oaxaca decomposition analysis, regarding demographic, socioeconomic, and health-related factors into the ‘explained’ component, by differences in individual attributes listed above, and the ‘unexplained’ component.

Results

Empirical analyses showed that women’s lower cognitive functioning was partly explained by the endowment effect. Moreover, a shorter duration of formal education and a larger proportion with their longest occupation being domestic worker accounted for steeper cognitive decline and more prevalent mild cognitive impairment in women than in men.

Conclusion

This empirical study suggested that gender differences in cognitive functioning and decline account for different individual attributes of social determinants among men and women. Particularly, men seem to be more engaged in activities which accumulate intellectual experiences through education and occupation, as suggested by the cognitive reserve hypothesis.
Application of the screening and indirect cohort methods to evaluate the effectiveness of pneumococcal vaccination program in adults 75 years and older in Taiwan
Authors: Su Wei-Ju , Chuang Pei-Hung , Chang Luan-Yin , Lo Hsiu-Yun , Chiang Chuen-Sheue , Wang Ez-Tzu , Yang Chin-Hui
Published: January 2021

Background

The Taiwanese national 23-valent pneumococcal polysaccharide vaccine (PPV23) program in adults ≥75 years of age and the 13-valent pneumococcal conjugate vaccine (PCV13) program for children were implemented in 2008 and 2013, respectively. In this study we evaluated PPV23 vaccine effectiveness (PPV23VE) in the elderly, with regard to both direct protection from the vaccine itself and the indirect protection conferred by PCV13 immunization in children.

Methods

The incidence of invasive pneumococcal disease (IPD) in Taiwan from July 2008 to June 2016 was collected from IPD surveillance data. A comparison of IPD incidence with a nationwide vaccination registry allowed an estimation of PPV23VE by the screening and indirect cohort methods.

Results

The incidence of IPD in adults ≥75 years of age ranged from 13.9 per 100,000 inhabitants during the period July 2008–June 2013 to 10.4 per 100,000 inhabitants between July 2013 and June 2016 (relative risk [RR]: 0.75; 95% confidence interval [95% CI]: 0.67–0.85). According to the screening method, PPV23VE against death within 30 days of IPD onset, all IPD, and PPV23-serotype IPD was 32.5% (95% CI: 17.5–44.7%), 33.9% (95% CI: 25.2–41.5%) and 43.4% (95% CI: 34.4–51.2%), respectively. PPV23VE with the indirect cohort method was 39.0% (95% CI: 15.5–55.9%) for all PPV23 serotypes and 71.5% (95% CI: 44.2–85.4%) for 11 serotypes included in PPV23 but not in PCV13. During the period July 2008–June 2012, PPV23VE against PPV23-serotype IPD was 55.1% (95% CI: 27.2–72.3%).

Conclusions

PPV23 is able to prevent IPD and 30-day fatality in adults 75 years of age and older due to a combination of direct effects from PPV23 and indirect effects from PCV13. It might confer higher protection against PPV23-serotype IPD before the introduction of PCV13 program in children.
The impact of antenatal care on under‐five mortality in Ethiopia: a difference‐in‐differences analysis
Authors: Oduse Samuel , Zewotir Temesgen , North Delia
Published: January 2021

Background

Sub-Saharan Africa, as opposed to other regions, has the highest under-five mortality rates yet makes the least improvement in reducing under-five mortality. Despite the decline, Ethiopia is among the top ten countries contributing the most to global under-five mortalities. This article examines the impact of the number of antenatal care and the timing of first antenatal care on child health outcomes. We specifically investigated if the utilization of antenatal care services positively affects the reduction of under-five mortality.

Methods

We employ a difference-in-differences design with propensity score matching to identify direct causal effects of antenatal care on under-five mortality based on the Ethiopian Demographic Health Survey data of 2011 and 2016. Our sample includes 22 295 women between the ages of 14–49 who had antenatal care visits at different times before delivery.

Results

The study revealed 1 481 cases of reported under-five mortality. 99.0% of that under-five mortality cases are women who had less than eight antenatal care visits, while only 1% of that is by women who had eight or more antenatal care visits. Antenatal care visit decreases the likelihood of under-five mortality in Ethiopia by 45.2% (CI = 19.2–71.3%, P-value < 0.001) while the timing of first antenatal care within the first trimester decreases the likelihood of under-five mortality by 10% (CI = 5.7–15.6%, P-value < 0.001).

Conclusions

To achieve a significant reduction in the under-five mortality rate, Intervention programs that encourages more antenatal care visits should be considered. This will improve child survival and help in attaining Sustainable Development Goal targets.
Asthma in elderly is characterized by increased sputum neutrophils, lower airway caliber variability and air trapping
Authors: Schleich F. , Graff S. , Guissard F. , Henket M. , Paulus V. , Louis R.
Published: January 2021

Background

Elderly asthmatics represent an important group that is often excluded from clinical studies. In this study we wanted to present characteristics of asthmatics older than 70 years old as compared to younger patients.

Methods

We conducted a retrospective analysis on a series of 758 asthmatics subdivided in three groups: lower than 40, between 40 and 70 and older than 70. All the patients who had a successful sputum induction were included in the study.

Results

Older patients had a higher Body Mass Index, had less active smokers and were more often treated with Long Acting anti-Muscarinic Agents. We found a significant increase in sputum neutrophil counts with ageing. There was no significant difference in blood inflammatory cell counts whatever the age group. Forced expiratory volume in one second (FEV1) and FEV1/FVC values were significantly lower in elderly who had lower bronchial hyperresponsiveness and signs of air trapping. We found a lower occurrence of the allergic component in advanced ages. Asthmatics older than 70 years old had later onset of the disease and a significant longer disease duration.

Conclusion

Our study highlights that asthmatics older than 70 years old have higher bronchial neutrophilic inflammation, a poorer lung function, signs of air trapping and lower airway variability. The role of immunosenescence inducing chronic low-grade inflammation in this asthma subtype remains to be elucidated.
Exploring the experiences of changes to support access to primary health care services and the impact on the quality and safety of care for homeless people during the COVID-19 pandemic: a study protocol for a qualitative mixed methods approach
Authors: Howells Kelly , Burrows Martin , Amp Mat , Brennan Rachel , Yeung Wan-Ley , Jackson Shaun , Dickinson Joanne , Draper Julie , Campbell Stephen , Ashcroft Darren , Blakeman Tom , Sanders Caroline
Published: January 2021

Background

Despite high level of health care need amongst people experiencing homelessness, poor access is a major concern. This is sometimes due to organisational and bureaucratic barriers, but also because they often feel stigmatised and treated badly when they do seek health care. The COVID-19 pandemic and the required social distancing measures have caused unprecedented disruption and change for the organisation of primary care, particularly for people experiencing homelessness. Against this backdrop there are many questions to address regarding whether the recent changes required to deliver services to people experiencing homelessness in the context of COVID-19 will help to address or compound problems in accessing care and inequalities in health outcomes.

Methods

An action led and participatory research methodology will be employed to address the study objectives. Interviews with people experiencing homelessness were will be conducted by a researcher with lived experience of homelessness. Researchers with lived experience are able to engage with vulnerable communities in an empathetic, non-judgemental way as their shared experience promotes a sense of trust and integrity, which in turn encourages participation in research and may help people speak more openly about their experience. The experiences of health professionals and stakeholders delivering and facilitating care for people experiencing homelessness during the pandemic will also be explored.

Discussion

It is important to explore whether recent changes to the delivery of primary care in response to the COVID-19 pandemic compromise the safety of people experiencing homelessness and exacerbate health inequalities. This could have implications for how primary healthcare is delivered to those experiencing homelessness not only for the duration of the pandemic but in the future.
Neuroinflammatory processes are augmented in mice overexpressing human heat-shock protein B1 following ethanol-induced brain injury
Authors: Dukay Brigitta , Walter Fruzsina R. , Vigh Judit P. , Barabási Beáta , Hajdu Petra , Balassa Tamás , Migh Ede , Kincses András , Hoyk Zsófia , Szögi Titanilla , Borbély Emőke , Csoboz Bálint , Horváth Péter , Fülöp Lívia , Penke Botond , Vígh László , Deli Mária A. , Sántha Miklós , Tóth Melinda E.
Published: January 2021

Background

Heat-shock protein B1 (HSPB1) is among the most well-known and versatile member of the evolutionarily conserved family of small heat-shock proteins. It has been implicated to serve a neuroprotective role against various neurological disorders via its modulatory activity on inflammation, yet its exact role in neuroinflammation is poorly understood. In order to shed light on the exact mechanism of inflammation modulation by HSPB1, we investigated the effect of HSPB1 on neuroinflammatory processes in an in vivo and in vitro model of acute brain injury.

Methods

In this study, we used a transgenic mouse strain overexpressing the human HSPB1 protein. In the in vivo experiments, 7-day-old transgenic and wild-type mice were treated with ethanol. Apoptotic cells were detected using TUNEL assay. The mRNA and protein levels of cytokines and glial cell markers were examined using RT-PCR and immunohistochemistry in the brain. We also established primary neuronal, astrocyte, and microglial cultures which were subjected to cytokine and ethanol treatments. TNFα and hHSPB1 levels were measured from the supernates by ELISA, and intracellular hHSPB1 expression was analyzed using fluorescent immunohistochemistry.

Results

Following ethanol treatment, the brains of hHSPB1-overexpressing mice showed a significantly higher mRNA level of pro-inflammatory cytokines (Tnf, Il1b), microglia (Cd68, Arg1), and astrocyte (Gfap) markers compared to wild-type brains. Microglial activation, and 1 week later, reactive astrogliosis was higher in certain brain areas of ethanol-treated transgenic mice compared to those of wild-types. Despite the remarkably high expression of pro-apoptotic Tnf, hHSPB1-overexpressing mice did not exhibit higher level of apoptosis. Our data suggest that intracellular hHSPB1, showing the highest level in primary astrocytes, was responsible for the inflammation-regulating effects. Microglia cells were the main source of TNFα in our model. Microglia isolated from hHSPB1-overexpressing mice showed a significantly higher release of TNFα compared to wild-type cells under inflammatory conditions.

Conclusions

Our work provides novel in vivo evidence that hHSPB1 overexpression has a regulating effect on acute neuroinflammation by intensifying the expression of pro-inflammatory cytokines and enhancing glial cell activation, but not increasing neuronal apoptosis. These results suggest that hHSPB1 may play a complex role in the modulation of the ethanol-induced neuroinflammatory response.
The safety of early versus late ileostomy reversal after low anterior rectal resection: a retrospective study in 47 patients
Authors: Fukudome Ian , Maeda Hiromichi , Okamoto Ken , Kuroiwa Hajime , Yamaguchi Sachi , Fujisawa Kazune , Shiga Mai , Dabanaka Ken , Kobayashi Michiya , Namikawa Tsutomu , Hanazaki Kazuhiro
Published: January 2021

Background

This study aimed to clarify the safety of early closure in diverting ileostomy with lower anterior rectal-cancer resection.

Methods

We retrospectively reviewed consecutive 47 patients who underwent diverting ileostomy with lower rectal-cancer resection between May 2009 and October 2017. The results of the stoma closure were compared between patients who underwent stoma closure within 90 days (early closure [EC] group) and those who underwent late closure (LC group; closure after 90 days). Because of the small sample size, the frequency of severe complications post closure was analyzed.

Results

Among 47 patients, 29 were in the EC group. Postoperative complications occurred in 48.3% (14/29) and 27.8% (5/18) of patients in the EC and LC groups, respectively. This difference was due to minor complications (Clavien-Dindo Classification I/II), such as superficial incisional surgical site infections (n=5) in the EC group. The rate of severe complications (Clavien-Dindo Classification ≥ III) was similar between the groups (20.7% vs. 16.7%, p=1, Fisher’s exact test).

Conclusions

No association was observed between the time of closure and development of major complications; however, there was an increased likelihood of minor complications after EC. This study provides a basis on which future treatment guidelines for early stoma closure may be developed without affecting patient quality of life.
Increased perioperative mortality for femoral neck fractures in patients with coronavirus disease 2019 (COVID-19): experience from the United Kingdom during the first wave of the pandemic
Authors: Wright Esther Victoria , Musbahi Omar , Singh Abhinav , Somashekar Naresh , Huber Christopher P. , Wiik Anatole Vilhelm
Published: January 2021

Background

The coronavirus disease 19 (COVID-19) pandemic has presented modern healthcare with an unprecedented challenge. At the peak of the pandemic, trauma and orthopaedic services at our institutions undertook internal restructuring, diverting resources to frontline medical care. Consequently, we sought to assess the impact on the elderly and comorbid patients presenting with femoral neck fractures, with a particular focus on 30-day mortality, length of stay, multidisciplinary team involvement and departmental structuring.

Method

A retrospective analysis of patients presenting with femoral neck fractures at three separate West London NHS Trusts was undertaken between March 11, 2020, to April 30, 2020. Length of stay, 30-day mortality and adherence to parameters constituting the best care evidence-based practice tariffs were compared between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive and negative patients. A similar comparison was also conducted between our cohort and the equivalent period in 2018 using data from the National Hip Fracture Database.

Results

A total of 68 patients presenting with femoral neck fractures were identified, mean age 81 (range 38–98), 73% female. There were 10 confirmed/suspected cases of COVID-19 on admission and a further seven confirmed as inpatients. The 30-day mortality within our cohort was 11.76% compared to 6% nationally in 2018 (p = 0.045). Orthogeriatric reviews occurred within 72 h in 71% of cases compared to 88% in the equivalent 2018 period. Within the cohort, mean length of stay was 17.13 days (SD 5.6, range 8-27 days) for SARS-CoV-2 positive patients compared to 10 days (SD 8.7, range 1–53 days) for negative patients (p < 0.05). Thirty-two patients (47%) required increased packages of care on discharge or rehabilitation.

Conclusions

The increase in 30-day mortality for SARS-CoV-2 positive patients presenting with femoral neck fractures is multifactorial, resulting from a combination of the direct effects of COVID-19 pneumonia as well as changes to the delivery of orthopaedic services. The provision of multidisciplinary care was directly affected by staff redeployment, particularly reorganisation of orthogeriatric services and lack of continuity of ward based clinical care. Our experiences have re-directed efforts towards the management of theatre teams, patient services and staffing, should we be faced with either a resurgence of COVID-19 or a future pandemic.
Burden of pneumococcal pneumonia requiring ICU admission in France: 1-year prognosis, resources use, and costs
Authors: Dupuis Claire , Sabra Ayman , Patrier Juliette , Chaize Gwendoline , Saighi Amine , Féger Céline , Vainchtock Alexandre , Gaillat Jacques , Timsit Jean-François
Published: January 2021

Background

Community-acquired pneumonia (CAP), especially pneumococcal CAP (P-CAP), is associated with a heavy burden of illness as evidenced by high rates of intensive care unit (ICU) admission, mortality, and costs. Although well-defined acutely, determinants influencing long-term burden are less known. This study assessed determinants of 28-day and 1-year mortality and costs among P-CAP patients admitted in ICUs.

Methods

Data regarding all hospital and ICU stays in France in 2014 were extracted from the French healthcare administrative database. All patients admitted in the ICU with a pneumonia diagnosis were included, except those hospitalized for pneumonia within the previous 3 months. The pneumococcal etiology and comorbidities were captured. All hospital stays were included in the cost analysis. Comorbidities and other factors effect on the 28-day and 1-year mortality were assessed using a Cox regression model. Factors associated with increased costs were identified using log-linear regression models.

Results

Among 182,858 patients hospitalized for CAP in France for 1 year, 10,587 (5.8%) had a P-CAP, among whom 1665 (15.7%) required ICU admission. The in-hospital mortality reached 22.8% at day 28 and 32.3% at 1 year. The mortality risk increased with age > 54 years, malignancies (hazard ratio (HR) 1.54, 95% CI [1.23–1.94], p = 0.0002), liver diseases (HR 2.08, 95% CI [1.61–2.69], p < 0.0001), and the illness severity at ICU admission. Compared with non-ICU-admitted patients, ICU survivors remained at higher risk of 1-year mortality. Within the following year, 38.2% (516/1350) of the 28-day survivors required at least another hospital stay, mostly for respiratory diseases. The mean cost of the initial stay was €19,008 for all patients and €11,637 for subsequent hospital stays within 1 year. One-year costs were influenced by age (lower in patients > 75 years old, p = 0.008), chronic cardiac (+ 11% [0.02–0.19], p = 0.019), and respiratory diseases (+ 11% [0.03–0.18], p = 0.006).

Conclusions

P-CAP in ICU-admitted patients was associated with a heavy burden of mortality and costs at one year. Older age was associated with both early and 1-year increased mortality. Malignant and chronic liver diseases were associated with increased mortality, whereas chronic cardiac failure and chronic respiratory disease with increased costs.

Trial registration

N/A (study on existing database)
Distinctive epigenomic alterations in NF1-deficient cutaneous and plexiform neurofibromas drive differential MKK/p38 signaling
Authors: Grit Jamie L. , Johnson Benjamin K. , Dischinger Patrick S. , J. Essenburg Curt , Adams Marie , Campbell Stacy , Pollard Kai , Pratilas Christine A. , Triche Tim J. , Graveel Carrie R. , Steensma Matthew R.
Published: January 2021

Benign peripheral nerve sheath tumors are the clinical hallmark of Neurofibromatosis Type 1. They account for substantial morbidity and mortality in NF1. Cutaneous (CNF) and plexiform neurofibromas (PNF) share nearly identical histology, but maintain different growth rates and risk of malignant conversion. The reasons for this disparate clinical behavior are not well explained by recent genome or transcriptome profiling studies. We hypothesized that CNFs and PNFs are epigenetically distinct tumor types that exhibit differential signaling due to genome-wide and site-specific methylation events. We interrogated the methylation profiles of 45 CNFs and 17 PNFs from NF1 subjects with the Illumina EPIC 850K methylation array. Based on these profiles, we confirm that CNFs and PNFs are epigenetically distinct tumors with broad differences in higher-order chromatin states and specific methylation events altering genes involved in key biological and cellular processes, such as inflammation, RAS/MAPK signaling, actin cytoskeleton rearrangement, and oxytocin signaling. Based on our identification of two separate DMRs associated with alternative leading exons inMAP2K3,we demonstrate differential RAS/MKK3/p38 signaling between CNFs and PNFs. Epigenetic reinforcement of RAS/MKK/p38 was a defining characteristic of CNFs leading to pro-inflammatory signaling and chromatin conformational changes, whereas PNFs signaled predominantly through RAS/MEK. Tumor size also correlated with specific CpG methylation events. Taken together, these findings confirm thatNF1deficiency influences the epigenetic regulation of RAS signaling fates, accounting for observed differences in CNF and PNF clinical behavior. The extension of these findings is that CNFs may respond differently than PNFs to RAS-targeted therapeutics raising the possibility of targeting p38-mediated inflammation for CNF treatment.
Targeting the RHOA pathway improves learning and memory in adult Kctd13 and 16p11.2 deletion mouse models
Authors: Martin Lorenzo Sandra , Nalesso Valérie , Chevalier Claire , Birling Marie-Christine , Herault Yann
Published: January 2021

Background

Gene copy number variants play an important role in the occurrence of neurodevelopmental disorders. Particularly, the deletion of the 16p11.2 locus is associated with autism spectrum disorder, intellectual disability, and several other features. Earlier studies highlighted the implication of Kctd13 genetic imbalance in 16p11.2 deletion through the regulation of the RHOA pathway.

Methods

Here, we generated a new mouse model with a small deletion of two key exons in Kctd13. Then, we targeted the RHOA pathway to rescue the cognitive phenotypes of the Kctd13 and 16p11.2 deletion mouse models in a pure genetic background. We used a chronic administration of fasudil (HA1077), an inhibitor of the Rho-associated protein kinase, for six weeks in mouse models carrying a heterozygous inactivation of Kctd13, or the deletion of the entire 16p11.2 BP4-BP5 homologous region.

Results

We found that the small Kctd13 heterozygous deletion induced a cognitive phenotype similar to the whole deletion of the 16p11.2 homologous region, in the Del/+ mice. We then showed that chronic fasudil treatment can restore object recognition memory in adult heterozygous mutant mice for Kctd13 and for 16p11.2 deletion. In addition, learning and memory improvement occurred in parallel to change in the RHOA pathway.

Limitations

The Kcdt13 mutant line does not recapitulate all the phenotypes found in the 16p11.2 Del/+ model. In particular, the locomotor activity was not altered at 12 and 18 weeks of age and the object location memory was not defective in 18-week old mutants. Similarly, the increase in locomotor activity was not modified by the treatment in the 16p11.2 Del/+ mouse model, suggesting that other loci were involved in such defects. Rescue was observed only after four weeks of treatment but no long-term experiment has been carried out so far. Finally, we did not check the social behaviour, which requires working in another hybrid genetic background.

Conclusion

These findings confirm KCTD13 as one target gene causing cognitive deficits in 16p11.2 deletion patients, and the relevance of the RHOA pathway as a therapeutic path for 16p11.2 deletion. In addition, they reinforce the contribution of other gene(s) involved in cognitive defects found in the 16p11.2 models in older mice.
Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy
Authors: Nammian Pegah , Asadi-Yousefabad Seyedeh-Leili , Daneshi Sajad , Sheikhha Mohammad Hasan , Tabei Seyed Mohammad Bagher , Razban Vahid
Published: January 2021

Introduction

Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment.

Methods

For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis.

Results

Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups.

Conclusions

Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.
Novel pharmacotherapy: NNI-362, an allosteric p70S6 kinase stimulator, reverses cognitive and neural regenerative deficits in models of aging and disease
Authors: Sumien Nathalie , Wells Matthew S. , Sidhu Akram , Wong Jessica M. , Forster Michael J. , Zheng Qiao-Xi , Kelleher-Andersson Judith A.
Published: January 2021

Aging is known to slow the neurogenic capacity of the hippocampus, one of only two mammalian adult neurogenic niches. The reduction of adult-born neurons with age may initiate cognitive decline progression which is exacerbated in chronic neurodegenerative disorders, e.g., Alzheimer’s disease (AD). With physiologic neurogenesis diminished, but still viable in aging, non-invasive therapeutic modulation of this neuron regeneration process remains possible. The discovery of truly novel neuron regenerative therapies could be identified through phenotypic screening of small molecules that promote adult-born neurons from human neural progenitor cells (hNPCs). By identifying neuron-generating therapeutics and potentially novel mechanism of actions, therapeutic benefit could be confirmed through in vivo proof-of-concept studies. The key aging and longevity mTOR/p70S6 kinase axis, a commonly targeted pathway, is substrate for potential selective kinase modulators to promote new hippocampal neurons from NPCs. The highly regulated downstream substrate of mTOR, p70S6 kinase, directly controls pleiotropic cellular activities, including translation and cell growth. Stimulating this kinase, selectively in an adult neurogenic niche, should promote NPC proliferation, and cell growth and survival in the hippocampus. Studies of kinase profiling and immunocytochemistry of human progenitor neurogenesis suggest that the novel small molecule NNI-362 stimulates p70S6 kinase phosphorylation, which, in turn, promotes proliferation and differentiation of NPCs to neurons. NNI-362 promoted the associative reversal of age- and disease-related cognitive deficits in aged mice and Down syndrome-modeled mice. This oral, allosteric modulator may ultimately be beneficial for age-related neurodegenerative disorders involving hippocampal-dependent cognitive impairment, specifically AD, by promoting endogenous hippocampal regeneration.