bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of physical training on cytokine expression in CD4+ T lymphocytes in subjects with stable COPD
Authors: Uzeloto Juliana S. , de Toledo-Arruda Alessandra C. , Silva Bruna S.A. , Braz Aline M.M. , de Lima Fabiano F. , Grigoletto Isis , Ramos Dionei , Golim Marjorie A. , Ramos Ercy M.C.
Published: June 2022

Introduction:

Although evidence suggests that physical exercise reduces systemic inflammation, at the plasma level, there are still contradictions in chronic obstructive pulmonary disease (COPD). In this sense, analysis of intracellular cytokines could clear off the effect of physical exercise on the inflammatory profile of these subjects.

Aim:

The aim was to evaluate the effect of physical training on cytokine expression in CD4+ T lymphocytes from subjects with COPD.

Methods:

This is a randomized controlled trial. Subjects with stable COPD were grouped into two groups, exercise and control. In total, 23 subjects with stable COPD were evaluated, of which 15 underwent aerobic strength training [physical exercise group (PEG)] and 8 underwent breathing exercises [respiratory physiotherapy group (RPG)]. Intracellular cytokines [interleukin (IL)-8, IL-13, IL-17, IL-6, IL-2, IL-10, and tumor necrosis factor alpha (TNF-α)] from CD4+ T lymphocytes were analyzed from peripheral blood through flow cytometry, before and after 8 weeks of intervention.

Results:

The PEG and RPG groups had a mean age of 68 ± 5.96 and 72.25 ± 6.86 years and predicted forced expiratory volume in the first second (FEV1) of 58.6 ± 15.99% and 39.75 ± 10.39%, respectively. It was possible to detect a significant reduction in IL-8 ( p = 0.0125) and an increase in IL-13 ( p = 0.0014) and an increase in TNF-α ( p < 0.001) in both groups.

Conclusion:

Eight weeks of physical training, both peripheral and respiratory, were able to reduce concentrations of IL-8 and to increase IL-13, and TNF-α in CD4+ T lymphocytes in subjects with stable COPD. The findings reinforce the benefits of interventions in subjects with COPD, revealing data not previously investigated.
SARS-CoV-2-inactivated vaccine hesitancy and the safety in inflammatory bowel disease patients: a single-center study
Authors: Cao Yubin , Feng Jiaming , Duan Shihao , Yang Yi , Zhang Yan
Published: June 2022

Background:

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine is thought to be the most effective preventive method of controlling the coronavirus disease 2019 (COVID-19) epidemic. Some patients with immune-related diseases, including inflammatory bowel disease (IBD) patients, however, may hesitate to be vaccinated for various reasons. Although several guidelines recommend vaccinating all IBD patients with inactivated SARS-CoV-2 vaccines, there is still a lack of real-world data on the safety of inactivated SARS-CoV-2 vaccines and COVID-19 vaccination rate in IBD patients. In this study, we investigated the reasons for hesitancy in COVID-19 vaccination, the COVID-19 vaccination rate, and the safety of SARS-CoV-2-inactivated vaccination in patients with IBD.

Methods:

This was a retrospective study. A total of 418 participants with IBD were enrolled to calculate the vaccination rates. A total of 232 patients with IBD who did not receive SARS-CoV-2 vaccination were recruited to investigate the reasons for hesitation. A follow-up survey of 151 IBD patients and 188 healthy participants who had received the SARS-CoV-2-inactivated vaccination was conducted to analyze adverse reactions.

Results:

The COVID-19 vaccination rate was 49.3% and almost half of the participants were ‘Concerned about the safety of the vaccine (such as adverse reactions) due to IBD’. After SARS-CoV-2 vaccination, adverse reactions were mild or moderate. The adverse reactions in the IBD and non-IBD populations were roughly the same, and IBD medications did not increase the risk of adverse reactions.

Conclusion:

SARS-CoV-2-inactivated vaccination rates in IBD patients are still low and a significant proportion of patients are hesitant about the vaccine because of safety concerns. SARS-CoV-2-inactivated vaccination in patients with IBD appears to be safe.
Treatment and care of women with epilepsy before, during, and after pregnancy: a practical guide
Authors: Nucera Bruna , Brigo Francesco , Trinka Eugen , Kalss Gudrun
Published: June 2022

Women with epilepsy (WWE) wishing for a child represent a highly relevant subgroup of epilepsy patients. The treating epileptologist needs to delineate the epilepsy syndrome and choose the appropriate anti-seizure medication (ASM) considering the main goal of seizure freedom, teratogenic risks, changes in drug metabolism during pregnancy and postpartum, demanding for up-titration during and down-titration after pregnancy. Folic acid or vitamin K supplements and breastfeeding are also discussed in this review. Lamotrigine and levetiracetam have the lowest teratogenic potential. Data on teratogenic risks are also favorable for oxcarbazepine, whereas topiramate tends to have an unfavorable profile. Valproate needs special emphasis. It is most effective in generalized seizures but should be avoided whenever possible due to its teratogenic effects and the negative impact on neuropsychological development of in utero-exposed children. Valproate still has its justification in patients not achieving seizure freedom with other ASMs or if a woman decides to or cannot become pregnant for any reason. When valproate is the most appropriate treatment option, the patient and caregiver must be fully informed of the risks associated with its use during pregnancies. Folate supplementation is recommended to reduce the risk of major congenital malformations. However, there is insufficient information to address the optimal dose and it is unclear whether higher doses offer greater protection. There is currently no general recommendation for a peripartum vitamin K prophylaxis. During pregnancy most ASMs (e.g. lamotrigine, oxcarbazepine, and levetiracetam) need to be increased to compensate for the decline in serum levels; exceptions are valproate and carbamazepine. Postpartum, baseline levels are reached relatively fast, and down-titration is performed empirically. Many ASMs in monotherapy are (moderately) safe for breastfeeding and women should be encouraged to do so. This review provides a practically oriented overview of the complex management of WWE before, during, and after pregnancy.
The Concept of Wealth (māl) in the Sharīʿah and Its Relation to Digital Assets
Authors: Rosele Muhammad Ikhlas , Muneem Abdul , Che Seman Azizi Bin , Abdullah Luqman Bin Haji , Binti Abdul Rahman Noor Naemah , Sukor Mohd Edil Bin Abd , Ali Abdul Karim Bin
Published: June 2022

The study aims to address the concept of wealth from the perspective of the Sharīʿah and its relationship to contemporary digital assets such as cryptocurrency (Bitcoin). The qualitative research approach is adopted for this research. The data is collected from several resources such as books, journal articles, reports, conferences papers, and websites. The data is analyzed through an explanatory research approach by providing scholars’ opinions and their arguments on the subject matter. The findings of this study show that Sharīʿah provides certain conditions to consider something as asset or currency from the Sharīʿah perspective. In regard to cryptocurrency (Bitcoin), the Sharīʿah rules vary based on the types of cryptocurrencies and whether cryptocurrency meets the conditions to be considered as currency or assets. Moreover, either cryptocurrency is an asset or currency, it should not contravene any Sharīʿah laws, such as ribā (interest) and gharar (uncertainty). Since Sharīʿah does not limit the currency to dirhams and dīnārs, Bitcoin can be considered as an alternative to the current currencies in a digital form. This would enable financial markets to move faster and secure transaction methods in the future. The policymakers might find this study beneficial to issue new guidelines and policy documents. The findings of the study might be interesting for cryptocurrency enthusiasts and investors to have a deeper understanding of cryptocurrency from the Sharīʿah viewpoint.
Lipoaspiration and Processing to Create Microfragmented Adipose Tissue
Authors: McGee Cally , Baria Michael R. , Gatewood Corey , Tiwari Maneesh , Vasileff W. Kelton , Lavender Chad
Published: June 2022

Background:

Orthobiologics are increasingly used to treat musculoskeletal (MSK) conditions. Adipose may be a useful source of autologous cells for orthobiologic interventions. The lipoaspiration and processing techniques necessary to obtain these cells are not traditionally taught in most orthopedic training programs. Therefore, the goal of this video is to review the technique for adipose harvest and preparation to create microfragmented adipose tissue (MFAT).

Indications:

Currently, all MFAT applications are off-label. In practice, this is most commonly used for osteoarthritis and tendon disease.

Technique Description:

After local anesthesia is administered, a 17-gauge trochar is inserted into the subcutaneous adipose, and tumescent solution is injected. After a 5-minute waiting period, a separate 17-gauge harvest trochar is attached to the Autopose double-syringe (Arthrex; Naples, Florida) and is inserted into the subcutaneous adipose. Lipoaspiration is performed by moving the harvest device back and forth in a fan-like pattern. After 20 mL of lipoaspirate has been harvested from the first site, the lipoaspiration process is repeated on the contralateral side. After 40 mL of lipoaspirate has been harvested, the device is removed and decanted for 3 to 5 minutes. Then, 10 mL of sterile saline solution is injected into the device using the Luer lock attachment. This rinse process is repeated a second time. Once the excess fluid has been removed, the device is capped, and the outer syringe is slowly pushed down to move the tissue through the resizing filter. The inner syringe is removed and contains the final MFAT product.

Discussion/Conclusion:

Lipoaspirate is a simple technique that can be performed in the clinic or operating room to create MFAT. This provides a unique population of autologous cells that may be beneficial for treating MSK pathology.
Hemodynamic changes associated with neuraxial anesthesia in pregnant women with covid 19 disease: a retrospective case-control study
Authors: Sangroula D. , Maggard B. , Abdelhaleem A. , Furmanek S. , Clemons V. , Marsili B. , Stikes R. , Hill M. , Sigdel A. , Clifford S. P. , Huang J. , Akca O. , Logsdon M. C.
Published: June 2022

Background

Neuraxial blocks is the recommended mode of analgesia and anesthesia in parturients with Coronavirus 19 (COVID-19). There is limited data on the hemodynamic responses to neuraxial blocks in COVID-19 patients. We aim to compare the hemodynamic responses to neuraxial blocks in COVID-19 positive and propensity-matched COVID-19 negative parturients.

Methods

We conducted retrospective, cross-sectional case–control study of hemodynamic changes associated with neuraxial blocks in COVID-19 positive parturients in a Tertiary care academic medical center. Fifty-one COVID-19 positive women confirmed by nasopharyngeal reverse transcription–polymerase chain reaction (RT-PCR), were compared with propensity-matched COVID negative controls (n = 51). Hemodynamic changes after neuraxial block were recorded by electronic medical recording system and analyzed using paired and unpaired T- test and Wilcoxon-Mann–Whitney Rank Sum tests. The primary outcome was ≥ 20% change in MAP and HR after neuraxial block placement.

Results

In the epidural group, 7% COVID-19 positive parturients had > 20% decrease in mean arterial pressure (MAP) from baseline compared to 15% COVID-19 negative parturients (P = 0.66). In the spinal group, 83% of COVID-19 positive parturients had a decrease in MAP more than 20% from baseline compared to 71% in control (P = 0.49). MAP drop of more than 40% occurred in 29% COVID positive parturients in the spinal group versus 17% in COVID-19 negative parturients (P = 0.5465). In COVID-19 positive spinal group, 54% required vasopressors whereas 38% in COVID-19 negative spinal group required vasopressors (P = 0.387). We found a significant correlation between body mass index (BMI) > 30 and hypotension in COVID ( +) parturient with odds ratio (8.63; 95% CI-1.93 – 37.21) (P = 0.007).

Conclusion

Incidence and severity of hypotension after neuraxial blocks were similar between COVID-19 positive and COVID-19 negative parturients. BMI > 30 was a significant risk factor for hypotension as described in preexisting literature, this correlation was seen in COVID-19 positive parturients. The likely reason for parturients with BMI > 30 in COVID negative patients not showing similar correlation, is that the sample size was small.
Clinical-pathological characteristics and prognostic factors for malignant peritoneal mesothelioma in the elderly
Authors: Pan Dan , Wang Mengyao , Liu Wencheng , Li Yan , Sang Lixuan , Chang Bing
Published: June 2022

Background

Malignant peritoneal mesothelioma (MPM) is a rare disease characterized by atypical symptoms, difficult diagnosis, variable course and poor prognosis, and it develops mainly in elderly individuals. The authors aimed to identify the clinical-pathological characteristics, prognosis, and prognostic factors in elderly MPM patients.

Methods

From the National Cancer Institute Surveillance Epidemiology End Results (SEER) database, 1492 patients with MPM from 1975 to 2016 were selected and divided into the elderly group (≥ 65) and the adult group (< 65). We compared the clinical-pathological characteristics and treatment methods of the elderly group (N = 665) and the adult group (N = 827). At the same time, we analysed specific selected clinicopathological parameters and prognostic factors for elderly MPM patients.

Results

Compared with the adult group, the elderly group had higher percentages of male patients (P = 0.017) and white patients (P = 0.043) and lower proportions of insured patients (P < 0.001) married patients (P < 0.001), patients with peritoneal tumours (P = 0.006) and patients who underwent surgery (P < 0.001) and chemotherapy (P < 0.001). There was a significant difference in the differentiation grade between the two groups (P = 0.003). Elderly patients had a shorter median survival time than adult patients (6 months vs. 19 months). Uninsured (hazard ratio (HR): 5.187, P = 0.005), sarcomatoid type (HR 3.913, P < 0.001), poorly differentiated (HR 3.900, P < 0.001), distant metastasis (HR 1.735, P = 0.001), no cancer-directed surgery (HR 1.733, P < 0.001), and no chemotherapy (HR 1.532, P < 0.001) were independently associated with poorer prognosis in elderly MPM patients.

Conclusion

Compared with adult patients, elderly MPM patients had a higher male ratio, poor differentiation and relatively conservative treatment. The cancer-specific survival (CSS) rate of elderly MPM patients was significantly lower than that of adult patients. Insurance status, histology type, differentiation grade, stage, surgery status, and chemotherapy status were all independent prognostic factors for elderly MPM patients.
The role of socio-demographic factors and physical functioning in the intra- and interpersonal variability of older adults’ sedentary time: an observational two-country study
Authors: Compernolle Sofie , Cerin Ester , Barnett Anthony , Zhang Casper J. P. , Van Cauwenberg Jelle , Van Dyck Delfien
Published: June 2022

Background

Insight into the variability of older adults’ sedentary time is needed to inform future interventions. The aim of this study was to examine the intra- and interpersonal variability in sedentary time, and the moderating role of socio-demographics, physical functioning and geographical location in this variability.

Methods

Cross-sectional data from 818 community-dwelling older adults (mean age: 74.8 years; 61.1%women) of the Active Lifestyle and the Environment in Chinese Seniors and Belgian Environmental Physical Activity Study in Seniors were used. An interview questionnaire was administered to collect socio-demographic information. The Short Physical Performance Battery was performed to evaluate physical functioning, and Actigraph GT3X( +) accelerometers were used to estimate sedentary time. Linear mixed models with random intercepts at the neighborhood, person and day levels examined the variability in sedentary time, and the moderating role of socio-demographics, physical functioning and geographical location within this variability.

Results

Most of the variance in accelerometry-assessed sedentary time was due to intrapersonal variability across periods of the day (72.4%) followed by interpersonal variability within neighborhoods (25.6%). Those who were older, men, lived in Hong Kong, and experienced a lower level of physical functioning were more sedentary than their counterparts. Sedentary time increased throughout the day, with highest levels of sedentary time observed between 6:00 and 9:00 pm. The patterns of sedentary time across times of the day differed by gender, educational attainment, age, physical functioning and/or geographical location. No significant differences were detected between week and weekend day sedentary time.

Conclusions

The oldest old, men, and those with functional limitations are important target groups for sedentary behavior interventions. As sedentary time was the highest in the evening future sedentary behavior intervention should pay particular attention to the evening hours. The variations in diurnal patterns of sedentary time between population subgroups suggest that personalized just-in-time adaptive interventions might be a promising strategy to reduce older adults’ sedentary time.
Association between dietary behaviors and depression in adolescent girls
Authors: Sangouni Abbas Ali , Beigrezaei Sara , Akbarian Shahab , Ghayour-Mobarhan Majid , Yuzbashian Emad , Salehi-Abargouei Amin , Ferns Gordon A. , Khayyatzadeh Sayyed Saeid
Published: June 2022

Background

The growing prevalence of depression has become a major public health problem. There is limited evidence regarding the relationship between dietary behaviors and depression. The present study was designed to evaluate the association between dietary behaviors and depression score.

Methods

A total of 933 Iranian adolescent girls aged 12 to 18 years were included in this cross-sectional study. Depression severity score was assessed using a validated Persian version of Beck’s depression inventory. Dietary behaviors were pre-defined and assessed in ten domains using a standard questionnaire. To investigate the association between dietary behaviors and depression score, the linear regression analysis in crude and adjusted models was used.

Results

67.7% of participants had no or minimal depression symptoms and 32.3% of participants were categorized with mild-to-severe depression symptoms. There were significant inverse relationships between main meal consumption (Beta: -0.141; 95% CI: − 3.644 to − 1.000; P = 0.001), snack consumption (Beta: -0.100; 95% CI: − 2.400 to − 0.317; P = 0.002), regular meal consumption (Beta: 0.23; 95% CI: 0.13–0.42; P = 0.001) and food chewing (Beta: -0.152; 95% CI: − 2.279 to − 0.753; P = 0.03) with depression score. These associations remained significant after adjustment for confounding variables. In addition, frequency of intra-meal fluid intake (Beta: 0.096; 95% CI: 0.288 to 1.535; P = 0.004) and spicy foods consumption (Beta: 0.076; 95% CI: 0.098 to 1.508; P = 0.02) were directly associated with depression score in the crude model. These significant relations were disappeared in full adjusted model. No significant association was found between breakfast consumption, intake of fried foods, chewing ability, and tooth loss with depression score (P > 0.05).

Conclusions

Significant associations were observed between specific eating behaviors with depression score. Prospective studies are needed to confirm these findings.
Nerve merging repair in the replantation of a severed limb with defects in multiple nerves: five cases and long-term follow-up
Authors: Ding Wenquan , Li Xueyuan , Chen Hong , Wang Xiaofeng , Zhou Danya , Wang Xin
Published: June 2022

Background

Repairing all nerves is challenging in cases of upper arm avulsion combined with defects in multiple nerves because the donor area for autogenous nerve transplantation is limited and the outcomes of long-segment allogeneic nerve transplantation are poor. Based on the principle of magnified nerve regeneration, we present a method called nerve merging repair, the feasibility of which needs to be confirmed in clinical practice.

Methods

The nerve merging repair method relies on the use of fewer proximal nerves to innervate more distal nerves and depends mainly on whether the radial nerve (RN) can repair itself. In the case of defects in multiple nerves precluding RN self-repair, median-(median + radial) (M-(M + R)) repair is performed. If the RN can undergo self-repair, median-(median + ulnar) (M-(M + U)) or ulnar-(ulnar + median) (U-(U + M)) is used to repair the three nerves. Five cases were included in the study and involved the analysis of joint motor function, muscle strength and sensory recovery of the affected limb.

Results

The replanted limb survived in all 5 cases. Follow-up visits were conducted with the patients for 51–80 months, during which they experienced satisfactory recovery of skin sensation, elbow flexion and extension and partial recovery of hand muscle strength.

Conclusions

To a certain extent, treatment with the nerve merging repair method improved the sensory and motor function of the affected limb and limited the loss of function of the donor nerve area. This intervention provides a new approach for repairing long-segment defects in multiple nerves caused by avulsion amputation of the upper limb.
Three-dimensional evaluation of hyoid bone position in nasal and mouth breathing subjects with skeletal Class I, and Class II
Authors: Mohamed Amin S. , Habumugisha Janvier , Cheng Bo , Zhao Minyue , Guo Yucheng , Zou Rui , Wang Fei
Published: June 2022

Background

This retrospective study investigated the effect of breathing pattern, skeletal class (Class I, Class II), and age on the hyoid bone position (HBP) in normodivergent subjects.

Methods

A total of 126 subjects (61 males, 65 females) aged 7–9 years and 10–12 years were scanned using cone-beam computed tomography (CBCT). All participants were classified according to the anteroposterior skeletal pattern into (Class I, Class II). Each skeletal group was further divided according to the breathing mode into mouth breathers (MB) and nasal breathers (NB). The HBP was measured accordingly. Independent sample t-test and Mann Whitney U test were used to detect significant differences between the groups, and binary logistic regression was used to identify MB predictive indicators.

Results

The breathing mode and skeletal class affected the vertical HBP in subjects with 7–9 years, while they affected the anteroposterior HBP in subjects with 10–12 years. Regarding the age effect, hyoid bone was located more anteriorly in the older NB subjects, and hyoid bone was more inferiorly in the older age group. A regression equation of the significant variables was formulated, C3-Me (P: 001, OR: 2.27), and H-EB (P: 0.046, OR: 1.16) were positively correlated with occurrence of MB.

Conclusion

There were significantly different HBPs among subjects with different anteroposterior skeletal classes, breathing modes, and age cohorts. Moreover, C3-Me, and H-EB were significant predictors and correlated with increased likelihood of being MB subject.
Eating behaviors, attitudes, and beliefs that contribute to overweight and obesity among women in Lilongwe City, Malawi: a qualitative study
Authors: Ndambo Myness Kasanda , Nyondo-Mipando Alinane Linda , Thakwalakwa Chrissie
Published: June 2022

Background

Obesity is increasingly a public health concern in low- and middle-income countries, including Malawi where 36% of women have body mass index in overweight/obese categories in urban areas. Eating behaviors, attitudes, and beliefs are associated with body size, but have not been studied in-depth in sub-Saharan African countries. This study therefore, explored eating behaviors, attitudes, and beliefs of women in Lilongwe, Malawi.

Methods

This was a descriptive ancillary qualitative study utilising in-depth interviews with 27 women (13 in normal weight range and 14 in overweight/obesity ranges) puporsively selected in Lilongwe City, Malawi from October to November 2017. The concept of data saturation guided data collection, and it was reached with the 27 interviewed participants when there was no new information coming from the participants. All interviews were conducted in the local language, transcribed verbatim, and translated into English. The transcripts were analysed manually using thematic content analysis.

Results

Majority of participants perceived overweight as an indication of good health such that with food affordability, women deliberately gain weight to demonstrate their good health. Most normal weight respondents said they ate less food than they wanted to because of financial constraints. Most women in overweight/obese ranges in our sample reported that they eat large portions and eat frequently due to the desire to portray a good image of their marital life since there is a societal expectation that when a woman is married, her weight should increase to show that the marriage is successful. The perceived contributors to weight gain include eating behaviors, feelings about weight gain, and gender roles and social expectations to gain weight.

Conclusion

Beliefs and attitudes related to eating behaviors may have contributed to women being in overweight range and should be considered in designing obesity prevention interventions targeting women in Malawi.
Assessment of electrocardiogram interpretation competency among healthcare professionals and students of Ardabil University of Medical Sciences: a multidisciplinary study
Authors: Amini Keyvan , Mirzaei Alireza , Hosseini Mirtohid , Zandian Hamed , Azizpour Islam , Haghi Yagoob
Published: June 2022

Background

Electrocardiogram (ECG) interpretation is a core clinical skill that helps to rapid diagnosis of potentially life-threatening diseases. Misinterpretation of the electrocardiogram can lead to inappropriate clinical decisions with adverse outcomes. The main aim of this survey was to assess the competency of electrocardiogram interpretation and related factors among healthcare professionals and students of Ardabil University of Medical Sciences.

Methods

This descriptive cross-sectional study included 323 staff and students of Ardabil University of Medical Sciences in northwestern Iran. Data were collected randomly from November to January 1400 using the Badell-Coll ECG Interpretation Competency Questionnaire and analyzed using SPSS V.14. Statistical analysis included descriptive statistics, independent t-test, ANOVA, Pearson correlation coefficient and multiple linear regression.

Results

The results showed that the mean and standard deviation of electrocardiogram interpretation competency of health professional staff and students was 5.13 ± 2.25 (maximum score = 10). The large number of participants wasn’t able to identify normal sinus rhythm (n = 251, 77.3%), acute myocardial infarction (n = 206, 63.8%) and pathological Q waves (n = 201, 62.2%). The results of multiple linear regression showed that the variables of education level, self-assessment of electrocardiogram interpretation competence, work experience, and type of hospital were able to predict the competence of ECG interpretation in participants.

Conclusions

Our findings showed that the participants’ level of electrocardiogram interpretation competency was low. Hence, regular, standard training and education are recommended. Also, managers and educators of the health system should consider the role of positive self-assessment and exposure to ECG interpretation in improving the competence of staff and students to interpret ECG.
Factor VII, EPCR, aPC Modulators: novel treatment for neuroinflammation
Authors: Golderman Valery , Ben-Shimon Marina , Maggio Nicola , Dori Amir , Gofrit Shany Guly , Berkowitz Shani , Qassim Lamis , Artan-Furman Avital , Zeimer Talya , Chapman Joab , Shavit-Stein Efrat
Published: June 2022

Background

Inflammation and coagulation are linked and pathogenic in neuroinflammatory diseases. Protease-activated receptor 1 (PAR1) can be activated both by thrombin, inducing increased inflammation, and activated protein C (aPC), inducing decreased inflammation. Modulation of the aPC-PAR1 pathway may prevent the neuroinflammation associated with PAR1 over-activation.

Methods

We synthesized a group of novel molecules based on the binding site of FVII/aPC to the endothelial protein C receptor (EPCR). These molecules modulate the FVII/aPC-EPCR pathway and are therefore named FEAMs—Factor VII, EPCR, aPC Modulators. We studied the molecular and behavioral effects of a selected FEAM in neuroinflammation models in-vitro and in-vivo.

Results

In a lipopolysaccharide (LPS) induced in-vitro model, neuroinflammation leads to increased thrombin activity compared to control (2.7 ± 0.11 and 2.23 ± 0.13 mU/ml, respectively, p = 0.01) and decreased aPC activity (0.57 ± 0.01 and 1.00 ± 0.02, respectively, p < 0.0001). In addition, increased phosphorylated extracellular regulated kinase (pERK) (0.99 ± 0.13, 1.39 ± 0.14, control and LPS, p < 0.04) and protein kinase B (pAKT) (1.00 ± 0.09, 2.83 ± 0.81, control and LPS, p < 0.0002) levels indicate PAR1 overactivation, which leads to increased tumor necrosis factor-alpha (TNF-α) level (1.00 ± 0.04, 1.35 ± 0.12, control and LPS, p = 0.02). In a minimal traumatic brain injury (mTBI) induced neuroinflammation in-vivo model in mice, increased thrombin activity, PAR1 activation, and TNF-α levels were measured. Additionally, significant memory impairment, as indicated by a lower recognition index in the Novel Object Recognition (NOR) test and Y-maze test (NOR: 0.19 ± 0.06, -0.07 ± 0.09, p = 0.03. Y-Maze: 0.50 ± 0.03, 0.23 ± 0.09, p = 0.02 control and mTBI, respectively), as well as hypersensitivity by hot-plate latency (16.6 ± 0.89, 12.8 ± 0.56 s, control and mTBI, p = 0.01), were seen. FEAM prevented most of the molecular and behavioral negative effects of neuroinflammation in-vitro and in-vivo, most likely through EPCR-PAR1 interactions.

Conclusion

FEAM is a promising tool to study neuroinflammation and a potential treatment for a variety of neuroinflammatory diseases.
Anti-IgLON5 antibodies cause progressive behavioral and neuropathological changes in mice
Authors: Ni You , Feng Yifan , Shen Dingding , Chen Ming , Zhu Xiaona , Zhou Qinming , Gao Yining , Liu Jun , Zhang Qi , Shen Yuntian , Peng Lisheng , Zeng Zike , Yin Dou , Hu Ji , Chen Sheng
Published: June 2022

Background

Anti-IgLON5 disease is a rare neurological disorder associated with autoantibodies against the neuronal cell adhesion protein, IgLON5. Cellular investigations with human IgLON5 antibodies have suggested an antibody-mediated pathogenesis, but whether human IgLON5 autoantibodies can induce disease symptoms in mice is yet to be shown. Moreover, the effects of anti-IgLON5 autoantibodies on neurons and the precise molecular mechanisms in vivo remain controversial.

Methods

We investigated the effects of anti-IgLON5 antibodies in vivo and evaluated their long-term effects. We used two independent passive-transfer animal models and evaluated the effects of the antibodies on mouse behaviors at different time points from day 1 until day 30 after IgG infusion. A wide range of behaviors, including tests of locomotion, coordination, memory, anxiety, depression and social interactions were established. At termination, brain tissue was analyzed for human IgG, neuronal markers, glial markers, synaptic markers and RNA sequencing.

Results

These experiments showed that patient’s anti-IgLON5 antibodies induced progressive and irreversible behavioral deficits in vivo. Notably, cognitive abnormality was supported by impaired average gamma power in the CA1 during novel object recognition testing. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies in the hippocampus of anti-IgLON5 IgG-injected mice, which persisted 30 days after the injection of patient’s antibodies was stopped. Microglial and astrocyte density was increased in the hippocampus of anti-IgLON5 IgG-injected mice at Day 30. Whole-cell voltage clamp recordings proved that anti-IgLON5 antibodies affected synaptic homeostasis. Further western blot investigation of synaptic proteins revealed a reduction of presynaptic (synaptophysin) and post-synaptic (PSD95 and NMDAR1) expression in anti-IgLON5 IgG-injected mice.

Conclusions

Overall, our findings indicated an irreversible effect of anti-IgLON5 antibodies and supported the pathogenicity of these antibodies in vivo.
Ontogeny of the elemental composition and the biomechanics of radular teeth in the chiton Lepidochitona cinerea
Authors: Krings Wencke , Brütt Jan-Ole , Gorb Stanislav N.
Published: June 2022

Background

The radula, a chitinous membrane with embedded teeth, is one important molluscan autapomorphy. In some taxa (Polyplacophora and Patellogastropoda) one tooth type (the dominant lateral tooth) was studied intensively in the last decades with regard to its mechanical properties, chemical and structural composition, and the relationship between these parameters. As the dominant lateral tooth is probably one of the best studied biological materials, it is surprising, that data on elements and mechanical properties of the other tooth types, present on a chiton radula, is lacking.

Results

We provide data on the elemental distribution and mechanical properties (hardness and elasticity, i.e. Young’s modulus) of all teeth from the Polyplacophora Lepidochitona cinerea (Linnaeus, 1767) [Chitonidae: Ischnochitonidae]. The ontogeny of elements, studied by energy-dispersive X-ray spectroscopy, and of the mechanical properties, determined by nanoindentation, was analysed in every individual tooth type. Additionally, we performed breaking stress experiments with teeth under dry and wet condition, highlighting the high influence of the water content on the mechanical behaviour of the radula. We thereby could determine the forces and stresses, teeth can resist, which were previously not studied in representatives of Polyplacophora. Overall, we were able to relate the mineral (iron, calcium) content with the mechanical parameters (hardness and Young’s modulus) and the breaking force and stress in every tooth type. This led to a better understanding of the relationship between structure, material, and function in radular teeth. Further, we aimed at determining the role of calcium for the mechanical behaviour of the teeth: we decalcified radulae by ethylene diamine tetra acetic acid and performed afterwards elemental analyses, breaking stress experiments, and nanoindentation. Among other things, we detected that wet and decalcified radular teeth could resist highest forces, since teeth have a higher range of bending motion leading to a higher capability of teeth to gain mechanical support from the adjacent tooth row. This indicates, that the tooth material is the result of a compromise between failure reduction and the ability to transfer forces onto the ingesta.

Conclusion

We present novel data on the elemental composition, mechanical properties, and the mechanical behaviour of chiton teeth, which allows conclusions about tooth function. We could also relate the parameters mentioned, which contributes to our understanding on the origins of mechanical property gradients and the processes reducing structural failure in radular teeth. Additionally, we add more evidence, that the elemental composition of radular is probably species-specific and could be used as taxonomic character.
A systematic review of pooled procurement of medicines and vaccines: identifying elements of success
Authors: Parmaksiz Koray , Pisani Elizabeth , Bal Roland , Kok Maarten Olivier
Published: June 2022

Introduction

Pooled procurement of health commodities has increasingly been promoted as a solution to reduce prices, increase availability, and achieve more efficient procurement processes. However, little is known about what is required to implement pooled procurement mechanisms successfully and how they function under specific circumstances. Therefore, the aim of this systematic review is to synthesize empirically grounded insights by identifying the elements that are essential for setting up and operating pooled procurement mechanisms of medicines and vaccines.

Methods

Our review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Scopus and Web of Science for empirical studies on pooled procurement of medicines and vaccines using various search terms. Publications were assessed based on predetermined eligibility criteria.

Results

Our initial search yielded 1596 publications, of which 44 were eventually included in our review. Most of the included articles focused on pooled procurement mechanisms that operated on a sub-national level (43%), procured a variety of products (38%), and were set up with the goal to contain costs (64%). The review identified several elements that are essential for pooled procurement mechanisms to function. We organized these elements around three key actors in the mechanism: buyers, the pooled procurement organization, and suppliers. To participate in pooled procurement, buyers need a sufficient level of technical capacity, financial capacity and compatible laws and regulations. To carry out pooled procurement, the pooled procurement organization needs sufficient financial capacity, technical capacity, and independent operations. To supply the mechanism with health commodities, suppliers need sufficient incentives, such as a sufficient market size and a prompt payment mechanism.

Conclusion

Pooled procurement mechanisms are very diverse. They differ in characteristics and organizational structures and are set up to achieve a variety of goals. While certain essential elements are more likely to increase successful implementation and functioning of pooled procurement mechanisms, the organizational structure must be aligned with the goals of the mechanism, and adapted to the local contextual environment.
Global burden of rheumatic heart disease: trends from 1990 to 2019
Authors: Ou Zejin , Yu Danfeng , Liang Yuanhao , Wu Jinhua , He Huan , Li Yongzhi , He Wenqiao , Gao Yuhan , Wu Fei , Chen Qing
Published: June 2022

Background

Rheumatic heart disease (RHD) is a critical public health issue worldwide, and its epidemiological patterns have changed over the decades. This article aimed to estimate the global trends of RHD, and attributable risks from 1990 to 2019.

Methods

Data on RHD burden were explored from the Global Burden of Disease Study 2019. Trends of the RHD burden were estimated using the estimated annual percentage change (EAPC) and age-standardized rate (ASR).

Results

During 1990–2019, increasing trends in the ASR of incidence and prevalence of RHD were observed worldwide, with the respective EAPCs of 0.58 (95% confidence interval [CI] 0.52 to 0.63) and 0.57 (95%CI 0.50 to 0.63). Meanwhile, increasing trends commonly occurred in low and middle Socio-Demographic Index (SDI) regions and countries. The largest increasing trends in the ASR of incidence and prevalence were seen in Fiji, with the respective EAPCs being 2.17 (95%CI 1.48 to 2.86) and 2.22 (95%CI 1.53 to 2.91). However, death and disability-adjusted life years (DALYs) due to RHD showed pronounced decreasing trends of ASR globally, in which the EAPCs were − 2.98 (95%CI − 3.03 to − 2.94) and − 2.70 (95%CI − 2.75 to − 2.65), respectively. Meanwhile, decreasing trends were also observed in all SDI areas and geographic regions. The largest decreasing trends of death were observed in Thailand (EAPC = − 9.55, 95%CI − 10.48 to − 8.61). Among the attributable risks, behavioral risk-related death and DALYs caused by RHD had pronounced decreasing trends worldwide and in SDI areas.

Conclusions

Pronounced decreasing trends of death and DALYs caused by RHD were observed in regions and countries from 1990 to 2019, but the RHD burden remains a substantial challenge globally. The results would inform the strategies for more effective prevention and control of RHD.
Evaluation of rotavirus vaccine administration among a 22q11.2DS patient population
Authors: McGregor Sophie , Boroditsky Matthew , Blanchard-Rohner Geraldine , Loock Christine , Jade Hildebrand Kyla
Published: June 2022

Background

22q11.2 Deletion Syndrome (22q11.2DS) can result in array of congenital abnormalities including immune dysfunction. International guidelines recommend immune evaluation of 22q11.2DS patients prior to live vaccine administration. A rotavirus vaccination program for infants aged 2 and 4 months was implemented in British Columbia (BC) in 2012. Adherence to immune workup recommendations prior to 2 months of age in patients with 22q11.2DS and adverse events following immunization is not known.

Methods

A retrospective chart review of children diagnosed with 22q11.2DS in BC from January 1, 2012 to January 1, 2019 was conducted. Demographic, clinical, laboratory, immunization data and adverse reactions to vaccines were obtained. International guidelines were used as a reference for adherence to immunologic workup recommendations.

Results

Forty-two children with 22q11.2DS were included. Immunization records were available for 39 children, and 22 (52.3%) received at least one dose of a live rotavirus vaccine. No adverse events following immunization were noted in clinical records. While 25 out of 27 (92.6%) of patients who received an immunological workup had a CD4 + lymphocyte count to qualify for safe administration of a live vaccination, only 12 (44%) received the Rotavirus vaccine. Of 22 infants diagnosed with 22q11.DS prior to 8 weeks of age, only ten (45.5%) received an immune workup before the rotavirus vaccine.

Conclusions

The majority of our infant cohort did not receive medical care consistent with international 22q11.2DS vaccination and immunological surveillance recommendations. More effective dissemination of 22q11.2DS guidelines and improved immunological assessment for infants with 22q11.2DS in BC is necessary.
Pheochromocytoma triggered by coronavirus disease 2019: a case report
Authors: Naghshineh Hoda , Hasanpour Amirhossein , Ziaei Naghmeh , Sadeghi Mahmoud , Meftah Neda
Published: June 2022

Background

Coronavirus disease 2019 is an infectious disease with many presentations, and many of its effects on the human body are still unknown. Pheochromocytoma is a neuroendocrine tumor that may occur sporadically or be a manifestation of a hereditary disease line multiple endocrine neoplasia type 2.

Case presentation

In this study, we report a case of an Iranian patient infected with coronavirus disease 2019, causing unusual presentations of pheochromocytoma, including myocarditis and cerebrovascular involvement.

Conclusions

We discovered a case of pheochromocytoma as an unusual presentation of COVID-19. In further investigations we also discovered thyroid medullary carcinoma and at the end MEN 2 syndrome was diagnosed. After proper treatment many symptoms were eliminated.
Language agnostic missing subtitle detection
Authors: Gupta Honey , Sharma Mayank
Published: June 2022

Subtitles are a crucial component of Digital Entertainment Content (DEC such as movies and TV shows) localization. With ever increasing catalog (≈ 2M titles) and localization expansion (30+ languages), automated subtitle quality checks becomes paramount. Being a manual creation process, subtitles can have errors such as missing transcriptions, out-of-sync subtitle blocks with the audio and incorrect translations. Such erroneous subtitles result in an unpleasant viewing experience and impact the viewership. Moreover, manual correction is laborious, highly costly and requires expertise of audio and subtitle languages. A typical subtitle correction process consists of (1) linear watch of the movie, (2) identification of time stamps associated with erroneous subtitle blocks, and (3) correcting procedure. Among the three, time taken to watch the entire movie by a human expert is the most time consuming step. This paper discusses the problem of missing transcription, where the subtitle blocks corresponding to some speech segments in the DEC are non-existent. We present a solution to augment human correction process by automatically identifying the timings associated with the non-transcribed dialogues in a language agnostic manner. The correction step can then be performed by either human-in-the-loop mechanism or automatically using neural transcription (speech-to-text in same language) and translation (text-to-text in different languages) engines. Our method uses a language agnostic neural voice activity detector (VAD) and an audio classifier (AC) trained explicitly on DEC corpora for better generalization. The method consists of three steps: first, we use VAD to identify the timings associated with dialogues (predicted speech blocks). Second, we refine those timings using the AC module by removing the timings associated with the leading and trailing non-speech segments identified as speech by VAD. Finally, we compare the predicted dialogue timings to the dialogue timings present in the subtitle file (subtitle speech blocks) and flag the missing transcriptions. We empirically demonstrate that the proposed method (a) reduces incorrect predicted missing subtitle timings by 10%, (b) improves the predicted missing subtitle timings by 2.5%, (c) reduces false positive rate (FPR) of overextending the predicted timings by 77%, and (d) improves the predicted speech block-level precision by a 119% over VAD baseline on a human-annotated dataset of missing subtitle speech blocks.
Pareto Z-eigenvalue inclusion theorems for tensor eigenvalue complementarity problems
Authors: Yang Ping , Wang Yiju , Wang Gang , Hou Qiuling
Published: June 2022

This paper presents some sharp Pareto Z-eigenvalue inclusion intervals and discusses the relationships among different Pareto Z-eigenvalue inclusion intervals for tensor eigenvalue complementarity problems. As an application, we propose a sufficient condition for identifying the strict copositivity of tensors. Some examples are provided to illustrate the obtained results.
Effect of intraoperative dexmedetomidine on postoperative cognitive functions of elderly patients undergoing total laryngectomy
Authors: El-Shamy Ahmed Mohamed , Zaghlol Amgad Abdel Mageed , Ghafar Mai Mahmoud Abdel , Hendawy Shimaa Rabea Abdel Qader , Tarabeah Gehan Abd Allah
Published: June 2022

Background

Postoperative cognitive dysfunction is commonly encountered after major surgical operations. This study was conducted to evaluate the effect of dexmedetomidine on neurocognitive dysfunction and postoperative recovery after total laryngectomy in the elderly population.

Results

Preoperative characteristics were comparable between the two groups. However, both sevoflurane consumption and recovery time were significantly decreased in the Dex group. Also, the time to first analgesic request and sedation level showed a significant improvement in the same group. The Dex group showed its superiority regarding most of the used cognitive tests. Although there was no significant difference between the two study groups regarding basal S100B, postoperative levels significantly decreased in the Dex group.

Conclusions

Dexmedetomidine administration is associated with a significant improvement of cognitive function after surgery in the elderly population. It is associated with a better analgesic and sedative profile along with decreased neurological inflammatory markers. However, the patient must be closely monitored for side effects like bradycardia and hypotension.